Details of the Researcher

PHOTO

Eiji Nemoto
Section
Graduate School of Dentistry
Job title
Associate Professor
Degree

  • 博士（歯学）（東北大学）

Education 1

  • Tohoku University　Faculty of Dentistry　歯学

    - 1989/03

Committee Memberships 10

  • 日本歯周病学会　研究委員会 委員

    2023/04 - Present

  • 日本歯周病学会　編集委員会 委員

    2017/04 - Present

  • 日本歯周病学会　評議員

    2008/04 - Present

  • 日本歯科保存学会　評議員

    2006/04 - Present

  • 日本歯科保存学会　学術用語委員会 委員

    2023/04 - 2025/03

  • 日本歯周病学会　研究委員会 委員

    2011/04 - 2020/03

  • 日本歯科保存学会　学術用語委員会 副委員長

    2017/04 - 2019/03

  • 日本歯周病学会　利益相反委員会 委員

    2017/04 - 2019/03

  • 日本歯周病学会　倫理委員会 委員

    2017/04 - 2019/03

  • 日本歯周病学会　若手研究者の集いワーキンググループ 委員

    2013/04 - 2018/03

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Professional Memberships 6

  • 日本歯科保存学会(1997/04-)

  • 日本歯周病学会(1990/04-)

  • IADR(2001/01-)

  • 日本炎症・再生医学会(1991/04-)

  • 日本歯周病学会(2008/04- 評議員)

  • The Japanese society of conservative dentistry(2006/04- )

︎Show all ︎Show first 5

Research Areas 1

  • Life sciences / Conservative dentistry and endodontics / Periodontological Dentistry

Awards 8

  1. 東北大学歯学会学術賞

    2019/06　東北大学大学院歯学研究科

  2. 第11回 日本歯周病学会学術賞

    2011/09/24　日本歯周病学会

  3. デンツプライ賞

    2010/09　日本歯科保存学会

  4. Excellent Young Investigator Award

    2009/01/16　The 3rd International Symposium for Interface Oral Health Science

  5. 上原記念生命科学財団研究奨励

    2004/03/11　上原記念生命科学財団研究会

  6. 武田科学振興財団一般研究奨励

    2003/07/04　武田科学振興財団

  7. 第７回 日本炎症・再生医学会奨励賞

    2001/07/02　日本炎症・再生医学会

  8. 第３回日本歯周病学会奨励賞

    1998/05/21　日本歯周病学会

Show all ︎Show 5

Papers 109

  1. Piezo1-mediated mechanotransduction in cementocytes via protein kinase B and p38 mitogen-activated protein kinase signaling Peer-reviewed

    Xiong K., Y. Sakisaka, T. Tenkumo, E. Nemoto, K. Maruyama, F. Muhammad, S. Suzuki, H. Tada, S. Yamada

    J. Dent.Sci.　in press　2025/08

    DOI： 10.1016/j.jds.2025.08.001 　

  2. A cross-sectional interventional study on the effects of periodontal treatment on periodontal inflamed surface area and masticatory efficiency values according to the 2018 periodontal status classification. International-journal

    Shinji Matsuda, Hiromichi Yumoto, Yasutaka Komatsu, Nanae Dewake, Takanori Iwata, Takatoshi Nagano, Toshiya Morozumi, Ryoma Goto, Satsuki Kato, Motozo Yamashita, Joichiro Hayashi, Satoshi Sekino, Akiko Yamashita, Keiko Yamashita, Atsutoshi Yoshimura, Tsutomu Sugaya, Shogo Takashiba, Yoichiro Taguchi, Eiji Nemoto, Tomoaki Shintani, Tsuyoshi Miyagawa, Hiromi Nishi, Noriyoshi Mizuno, Yukihiro Numabe, Hiroyuki Kawaguchi

    BMC oral health　25　(1)　1094-1094　2025/07/04

    DOI： 10.1186/s12903-025-06456-7 　

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    BACKGROUND: Periodontal inflamed surface area (PISA) and masticatory efficiency have been used to evaluate the relationship between systemic diseases and oral diseases. However, clear standards for PISA values and masticatory efficiency in relation to the severity of periodontitis are lacking. This study aims to evaluate PISA values and masticatory efficiency based on the 2018 periodontal status classification system. METHODS: In total, 153 healthy participants diagnosed with periodontitis were included in the study. The diagnosis was based on the 2018 periodontal status classification. PISA values and masticatory efficiency were measured at baseline and after initial periodontal therapy. RESULTS: PISA demonstrated a higher area under the curve for Stage III (0.815) and Grade B (0.85). At baseline, PISA was showed significant negative correlation with masticatory efficiency (B coefficient [95% CI]: -0.02 [-0.03, -0.006], p < 0.01). Following periodontal therapy, both PISA values and masticatory efficiency showed significant improvements, with median PISA values changing from 856 at baseline to 277.5 after treatment, and mean masticatory efficiency increasing from 153.3 to 166.9. After initial periodontal therapy, PISA values were significantly higher in patients classified as Stage IV and Grade C compared to those with other stages and grades. Age exhibited a significant negative correlation with changes in PISA (B coefficient [95%CI]: -11.8 [-20.3, -3.19]), and change in PISA value was significantly positively related to the increase in masticatory efficiency (B coefficient [95%CI], 0.02 [(0.0002, 0.03]). In patients with periodontitis, changes in periodontitis classification were associated with increased PISA values and decreased masticatory efficiency. CONCLUSION: Periodontal therapy improved PISA and masticatory efficiency values. However, the extent of improvement was less pronounced in patients with higher stages and grades of periodontitis. It is essential to consider the interplay between increased PISA and decreased masticatory efficiency when treating patients with severe periodontitis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12903-025-06456-7.

  3. 最先端医療の今 メカニカルストレスを応用した新規歯周組織再生治療への挑戦

    丸山 顕太郎, 向阪 幸彦, 根本 英二, 山田 聡

    Medical Science Digest　50　(14)　794-798　2024/12

    Publisher: (株)ニュー・サイエンス社

    ISSN： 1347-4340

  4. Dynamic changes in chromatin accessibility during the differentiation of dental pulp stem cells reveal that induction of odontogenic gene expression is linked with specific enhancer construction

    Kento Sasaki, Shigeki Suzuki, Rahmad Rifqi Fahreza, Eiji Nemoto, Satoru Yamada

    Journal of Dental Sciences　19　(3)　1705-1713　2024/07

    DOI： 10.1016/j.jds.2023.10.022 　

    ISSN： 1991-7902

    eISSN： 2213-8862

  5. The histone deacetylase inhibitor MS-275 enhances the matrix mineralization of dental pulp stem cells by inducing fibronectin expression

    Shigeki Suzuki, Kento Sasaki, Rahmad Rifqi Fahreza, Eiji Nemoto, Satoru Yamada

    Journal of Dental Sciences　19　(3)　1680-1690　2024/07

    DOI： 10.1016/j.jds.2023.11.019 　

    ISSN： 1991-7902

    eISSN： 2213-8862

  6. Periodontal inflammation potentially inhibits hepatic cytochrome P450 expression and disrupts the omega-3 epoxidation pathway in a murine model International-journal

    Yoshino Daidouji, Shigeki Suzuki, Xiuting Wang, Rahmad Rifqi Fahreza, Eiji Nemoto, Satoru Yamada

    Journal of Dental Sciences　20　(1)　444-451　2024/05

    Publisher: Elsevier BV

    DOI： 10.1016/j.jds.2024.05.028 　

    ISSN： 1991-7902

  7. Effect of Periodontal Treatment on Reducing Chronic Inflammation in Systemically Healthy Patients With Periodontal Disease

    Shinji Matsuda, Tomoaki Shintani, Tsuyoshi Miyagawa, Hiromichi Yumoto, Yasutaka Komatsu, Nanae Dewake, Takanori Iwata, Takatoshi Nagano, Toshiya Morozumi, Ryoma Goto, Satsuki Kato, Masahiro Kitamura, Kitetsu Shin, Satoshi Sekino, Akiko Yamashita, Keiko Yamashita, Atsutoshi Yoshimura, Tsutomu Sugaya, Shogo Takashiba, Yoichiro Taguchi, Eiji Nemoto, Hiromi Nishi, Noriyoshi Mizuno, Yukihiro Numabe, Hiroyuki Kawaguchi

    The American Journal of Medicine　137　(3)　273-279.e2　2024/03

    Publisher: Elsevier BV

    DOI： 10.1016/j.amjmed.2023.11.001 　

    ISSN： 0002-9343

  8. Cementocyte-derived extracellular vesicles regulate osteoclastogenesis and osteoblastogenesis Peer-reviewed

    Jiajun Li, Yukihiko Sakisaka, Eiji Nemoto, Kentaro Maruyama, Shigeki Suzuki, Kaixin Xiong, Hiroyuki Tada, Taichi Tenkumo, Satoru Yamada

    Journal of Dental Sciences　2024/03

    Publisher: Elsevier BV

    DOI： 10.1016/j.jds.2024.02.025 　

    ISSN： 1991-7902

  9. Neutrophil extracellular traps inhibit osteoclastogenesis. International-journal

    Kento Numazaki, Hiroyuki Tada, Takashi Nishioka, Eiji Nemoto, Kenji Matsushita, Itaru Mizoguchi, Shunji Sugawara

    Biochemical and biophysical research communications　705　149743-149743　2024/02/29

    DOI： 10.1016/j.bbrc.2024.149743 　

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    Neutrophil extracellular traps (NETs) released by neutrophils upon inflammation or infection, act as an innate immune defense against pathogens. NETs also influence inflammatory responses and cell differentiation in host cells. Osteoclasts, which are derived from myeloid stem cells, are critical for the bone remodeling by destroying bone. In the present study, we explores the impact of NETs, induced by the inflammatory agent calcium ionophore A23187, on the differentiation and activation of osteoclasts, potentially through suppressing RANK expression. Our results collectively suggested that the inhibition of RANKL-mediated osteoclastogenesis by NETs might lead to the suppression of excessive bone resorption during inflammation.

  10. Periodontal ligament fibroblasts utilize isoprenoid intermediate farnesyl diphosphate for maintaining osteo/cementogenic differentiation abilities International-journal

    Xiuting Wang, Shigeki Suzuki, Hang Yuan, Shizu Hirata-Tsuchiya, Rahmad Rifqi Fahreza, Eiji Nemoto, Hideki Shiba, Satoru Yamada

    Journal of Dental Sciences　20　(1)　560-568　2024

    DOI： 10.1016/j.jds.2024.04.025 　

    ISSN： 1991-7902

    eISSN： 2213-8862

  11. Procyanidin B2 enhances anti-inflammatory responses of periodontal ligament cells by inhibiting the dominant negative pro-inflammatory isoforms of peroxisome proliferator-activated receptor γ

    Tadahiro Yamamoto, Hang Yuan, Shigeki Suzuki, Eiji Nemoto, Masahiro Saito, Satoru Yamada

    Journal of Dental Sciences　2023/10

    Publisher: Elsevier BV

    DOI： 10.1016/j.jds.2023.09.027 　

    ISSN： 1991-7902

  12. CBCTを基準とした側枝検出可能な電気的根管長測定器の検出能力に関する臨床的研究

    庄司 茂, 丸山 顕太郎, 須藤 圭一, 根本 英二

    日本歯内療法学会雑誌　44　(3)　209-213　2023/09

    Publisher: (一社)日本歯内療法学会

    ISSN： 1347-8672

    eISSN： 2423-9429

  13. Chromatin Accessibility Analysis Reveals Functional Transcription Factors and Regulators in Dental Pulp Stem Cell Differentiation

    Shigeki SUZUKI, Ryu HASEGAWA, Akiko SATO, Yoshino DAIDOUJI, Karin NAGASAKI, Eiji NEMOTO, Satoru YAMADA

    The Japanese Journal of Conservative Dentistry　66　(3)　179-191　2023/06/30

    Publisher: The Japanese Society of Conservative Dentistry

    DOI： 10.11471/shikahozon.66.179 　

    ISSN： 0387-2343

    eISSN： 2188-0808

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    Purpose: An increase in chromatin accessibility arises from the stretched chromatin structure, which enables the association of transcription complexes with local genomic DNA, and thus induces target mRNA transcription. This is one of the main molecular frameworks for epigenetic regulation of gene expression. In this study, the changes in whole-genomic chromatin accessibility that occur during induced differentiation of human dental pulp stem cells (hDPSC) were analyzed by assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq).  Methods: hDPSC were cultured in a mineralization induction medium. ATAC-seq samples were prepared before and after the 12-day culture. Bioinformatics analyses were conducted, involving open chromatin peak extraction, sample comparison, consensus DNA binding (CDB) sequence identification, and gene ontology (GO) analysis of neighboring genes for each peak.  Results: The bioinformatics analyses identified 45,493 and 45,370 open chromatin peaks at day 0 and day 12, respectively. The CDB sequences of transcription factors, including TEADs, bZIPs, and RUNXs, and insulators, including CTCF and BORIS, were commonly enriched in these peaks. Furthermore, GO analysis of neighboring genes of CTCF-CDB revealed an accumulation of the genes associated with the Hippo signaling pathway, in which TEADs act as the essential transcription factors, at day 12 but not at day 0. Additionally, the gene loci of the odonto/osteogenic genes, such as BMP2 and BMPR1B, were identified as accessible chromatin regions controlled by CTCF-CDB at day 12 but not at day 0. From these results, the types of CDB in the stretched chromatin region were not drastically changed before and after hDPSC differentiation. However, because CTCF participates in the dynamic genomic organization to regulate local chromatin accessibility and restrict the territory of distal enhancers and suppressors, CTCF aids TEADs in finding and associating with odonto/osteogenic gene loci, inducing odonto/osteogenic gene expression during differentiation.  Conclusion: Bioinformatics analysis indicated that local epigenetic alteration mediated by the insulators may play pivotal roles in hDPSC differentiation, and therefore, chromatin accessibility modulation may have therapeutic potential for inducing odontogenic differentiation of hDPSC.

  14. Macrophage migration inhibitory factor-mediated mast cell extracellular traps induce inflammatory responses upon Fusobacterium nucleatum infection Peer-reviewed

    Hiroyuki Tada, Takashi Nishioka, Rina Ishiyama, Li-Ting Song, Sakura Onoue, Kazuyoshi Kawahara, Eiji Nemoto, Kenji Matsushita, Shunji Sugawara

    <B>Biochemical and Biophysical Research Communications<B>, in press　2023/06

    DOI： 10.1016/j.bbrc.2023.06.060 　

  15. 歯髄幹細胞分化過程におけるクロマチンアクセシビリティ解析

    鈴木 茂樹, 佐藤 瞭子, 大道寺 美乃, 長崎 果林, 長谷川 龍, 根本 英二, 山田 聡

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集　158回　113-113　2023/05

    Publisher: (NPO)日本歯科保存学会

  16. 実験的歯周炎 歯周組織再生モデルにおける歯周組織エピゲノム変化の解析

    大道寺 美乃, 鈴木 茂樹, 佐藤 瞭子, 山本 真豊, 佐々木 健人, 王 秀てい, 長崎 果林, Fahreza Rahmad Rifqi, 長谷川 龍, 根本 英二, 山田 聡

    日本歯周病学会会誌　65　(春季特別)　125-125　2023/04

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

    eISSN： 1880-408X

  17. Introduction of tenomodulin by gene transfection vectors for rat bone tissue regeneration

    Han Wang, Taichi Tenkumo, Eiji Nemoto, Yoshiaki Kanda, Toru Ogawa, Keiichi Sasaki

    Regenerative Therapy　22　99-108　2023/03

    DOI： 10.1016/j.reth.2022.12.008 　

    eISSN： 2352-3204

  18. Serial Cultivation of an MSC-Like Cell Line with Enzyme-Free Passaging Using a Microporous Titanium Scaffold. International-journal

    Yukihiko Sakisaka, Hiroshi Ishihata, Kentaro Maruyama, Eiji Nemoto, Shigeki Chiba, Masaru Nagamine, Hiroshi Hasegawa, Takeshi Hatsuzawa, Satoru Yamada

    Materials (Basel, Switzerland)　16　(3)　2023/01/30

    DOI： 10.3390/ma16031165 　

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    In vitro studies on adherent cells require a process of passage to dissociate the cells from the culture substrate using enzymes or other chemical agents to maintain cellular activity. However, these proteolytic enzymes have a negative influence on the viability and phenotype of cells. The mesenchymal stem cell (MSC)-like cell line, C3H10T1/2, adhered, migrated, and proliferated to the same extent on newly designed microporous titanium (Ti) membrane and conventional culture dish, and spontaneous transfer to another substrate without enzymatic or chemical dissociation was achieved. The present study pierced a 10 μm-thick pure Ti sheet with 25 μm square holes at 75 μm intervals to create a dense porous structure with biomimetic topography. The pathway of machined holes allowed the cells to access both sides of the membrane frequently. In a culture with Ti membranes stacked above- and below-seeded cells, cell migration between the neighboring membranes was confirmed using the through-holes of the membrane and contact between the membranes as migration routes. Furthermore, the cells on each membrane migrated onto the conventional culture vessel. Therefore, a cell culture system with enzyme-free passaging was developed.

  19. Pharmacological Activation of YAP/TAZ by Targeting LATS1/2 Enhances Periodontal Tissue Regeneration in a Murine Model Peer-reviewed

    Akiko Sato, Shigeki Suzuki, Hang Yuan, Rahmad Fahreza, Xiuting Wang, Eiji Nemoto, Masahiro Saito, Satoru Yamada

    International Journal of Molecular Sciences　24　(2)　2023/01/04

    DOI： 10.3390/ijms24020970 　

    ISSN： 1661-6596

    eISSN： 1422-0067

  20. Hericium erinaceus ethanol extract and ergosterol exert anti-inflammatory activities by neutralizing lipopolysaccharide-induced pro-inflammatory cytokine production in human monocytes

    Hiroyuki Tada, Kazuyoshi Kawahara, Hiraku Osawa, Li-Ting Song, Kento Numazaki, Junya Kawai, Sakura Onoue, Takashi Nishioka, Eiji Nemoto, Kenji Matsushita, Shunji Sugawara

    Biochemical and Biophysical Research Communications　636　1-9　2022/12

    Publisher: Elsevier BV

    DOI： 10.1016/j.bbrc.2022.10.090 　

    ISSN： 0006-291X

  21. メカノレスポンス受容機構活性化による歯周組織再生

    佐藤 瞭子, 鈴木 茂樹, 山本 真豊, 佐々木 健人, 大道寺 美乃, 根本 英二, 齋藤 正寛, 山田 聡

    日本歯周病学会会誌　64　(秋季特別)　110-110　2022/08

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

    eISSN： 1880-408X

  22. 新規PPARγアゴニストprocyanidin B2による歯周炎発症抑制とPPARγ遺伝子座転写産物の関与

    山本 真豊, 鈴木 茂樹, 佐藤 瞭子, 佐々木 健人, 大道寺 美乃, 根本 英二, 斎藤 正寛, 山田 聡

    日本歯周病学会会誌　64　(秋季特別)　113-113　2022/08

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

    eISSN： 1880-408X

  23. セメント芽細胞由来エクソソームによる破骨細胞分化制御 RANKL誘導性破骨細胞形成に対する増強作用

    佐藤 令, 丸山 顕太郎, 根本 英二, 向阪 幸彦, 鈴木 茂樹, 黎 家君, 沼崎 研人, 多田 浩之, 山田 聡

    日本歯周病学会会誌　64　(秋季特別)　129-129　2022/08

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

    eISSN： 1880-408X

  24. メカノレスポンス受容機構活性化による歯周組織再生

    佐藤 瞭子, 鈴木 茂樹, 山本 真豊, 佐々木 健人, 大道寺 美乃, 根本 英二, 齋藤 正寛, 山田 聡

    日本歯周病学会会誌　64　(秋季特別)　110-110　2022/08

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

    eISSN： 1880-408X

  25. 新規PPARγアゴニストprocyanidin B2による歯周炎発症抑制とPPARγ遺伝子座転写産物の関与

    山本 真豊, 鈴木 茂樹, 佐藤 瞭子, 佐々木 健人, 大道寺 美乃, 根本 英二, 斎藤 正寛, 山田 聡

    日本歯周病学会会誌　64　(秋季特別)　113-113　2022/08

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

    eISSN： 1880-408X

  26. セメント芽細胞由来エクソソームによる破骨細胞分化制御 RANKL誘導性破骨細胞形成に対する増強作用

    佐藤 令, 丸山 顕太郎, 根本 英二, 向阪 幸彦, 鈴木 茂樹, 黎 家君, 沼崎 研人, 多田 浩之, 山田 聡

    日本歯周病学会会誌　64　(秋季特別)　129-129　2022/08

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

    eISSN： 1880-408X

  27. 歯周病リスク予測に向けた口腔状態と全身疾患関係性解明の後ろ向き研究

    向阪 幸彦, 佐々木 健人, 岩崎 麻美, 大谷 栄毅, 佐藤 瞭子, 山本 真豊, 佐藤 令, 栗田 真夏, 日原 大貴, 佐々木 啓一, 阿山 晴取, アマール・シュジャアデイン, 石川 有紀, 根本 英二, 山田 聡

    日本歯周病学会会誌　64　(春季特別)　122-122　2022/05

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

    eISSN： 1880-408X

  28. 歯周病リスク予測に向けた口腔状態と全身疾患関係性解明の後ろ向き研究

    向阪 幸彦, 佐々木 健人, 岩崎 麻美, 大谷 栄毅, 佐藤 瞭子, 山本 真豊, 佐藤 令, 栗田 真夏, 日原 大貴, 佐々木 啓一, 阿山 晴取, アマール・シュジャアデイン, 石川 有紀, 根本 英二, 山田 聡

    日本歯周病学会会誌　64　(春季特別)　122-122　2022/05

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

    eISSN： 1880-408X

  29. Loss of IκBζ Drives Dentin Formation via Altered H3K4me3 Status

    H. Yuan, S. Suzuki, H. Terui, S. Hirata-Tsuchiya, E. Nemoto, K. Yamasaki, M. Saito, H. Shiba, S. Aiba, S. Yamada

    Journal of Dental Research　101　(8)　951-961　2022/02/22

    Publisher: SAGE Publications

    DOI： 10.1177/00220345221075968 　

    ISSN： 0022-0345

    eISSN： 1544-0591

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    Enforced enrichment of the active promoter marks trimethylation of histone H3 lysine 4 (H3K4me3) and acetylation of histone H3 lysine 27 (H3K27ac) by inhibiting histone demethylases and deacetylases is positively associated with hard tissue formation through the induction of osteo/odontogenic differentiation. However, the key endogenous epigenetic modulator of odontoblasts to regulate the expression of genes coding dentin extracellular matrix (ECM) proteins has not been identified. We focused on nuclear factor (NF)–κB inhibitor ζ (IκBζ), which was originally identified as the transcriptional regulator of NF-κB and recently regarded as the NF-κB–independent epigenetic modulator, and found that IκBζ null mice exhibit a thicker dentin width and narrower pulp chamber, with aged mice having more marked phenotypes. At 6 mo of age, dentin fluorescent labeling revealed significantly accelerated dentin synthesis in the incisors of IκBζ null mice. In the molars of IκBζ null mice, marked tertiary dentin formation adjacent to the pulp horn was observed. Mechanistically, the expression of COL1A2 and COL1A1 collagen genes increased more in the odontoblast-rich fraction of IκBζ null mice than in wild type in vivo, similar to human odontoblast-like cells transfected with small interfering RNA for IκBζ compared with cells transfected with control siRNA in vitro. Furthermore, the direct binding of IκBζ to the COL1A2 promoter suppressed COL1A2 expression and the local active chromatin status marked by H3K4me3. Based on whole-genome identification of H3K4me3 enrichment, ECM and ECM organization–related gene loci were selectively activated by the knockdown of IκBζ, which consistently resulted in the upregulation of these genes. Collectively, this study suggested that IκBζ is the key negative regulator of dentin formation in odontoblasts by inhibiting dentin ECM- and ECM organization–related gene expression through an altered local chromatin status marked by H3K4me3. Therefore, IκBζ is a potential target for epigenetically improving the clinical outcomes of dentin regeneration therapies such as pulp capping.

  30. Extracellular Vesicles Derived From Murine Cementoblasts Possess the Potential to Increase Receptor Activator of Nuclear Factor-κB Ligand-Induced Osteoclastogenesis. International-journal Peer-reviewed

    Rei Sato, Kentaro Maruyama, Eiji Nemoto, Yukihiko Sakisaka, Shigeki Suzuki, Jiajun Li, Kento Numazaki, Hiroyuki Tada, Satoru Yamada

    Frontiers in physiology　13　825596-825596　2022

    DOI： 10.3389/fphys.2022.825596 　

    eISSN： 1664-042X

  31. Porphyromonas gingivalis Gingipains-Mediated Degradation of Plasminogen Activator Inhibitor-1 Leads to Delayed Wound Healing Responses in Human Endothelial Cells. International-journal

    Li-Ting Song, Hiroyuki Tada, Takashi Nishioka, Eiji Nemoto, Takahisa Imamura, Jan Potempa, Chang-Yi Li, Kenji Matsushita, Shunji Sugawara

    Journal of innate immunity　1-14　2021/11/25

    DOI： 10.1159/000519737 　

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    Plasminogen activator inhibitor-1 (PAI-1), a serine protease inhibitor, is constitutively produced by endothelial cells and plays a vital role in maintaining vascular homeostasis. Chronic periodontitis is an inflammatory disease characterized by bleeding of periodontal tissues that support the tooth. In this study, we aimed to determine the role of PAI-1 produced by endothelial cells in response to infections caused by the primary periodontal pathogen Porphyromonas gingivalis. We demonstrated that P. gingivalis infection resulted in significantly reduced PAI-1 levels in human endothelial cells. This reduction in PAI-1 levels could be attributed to the proteolysis of PAI-1 by P. gingivalis proteinases, especially lysine-specific gingipain-K (Kgp). We demonstrated the roles of these degradative enzymes in the endothelial cells using a Kgp-specific inhibitor and P. gingivalis gingipain-null mutants, in which the lack of the proteinases resulted in the absence of PAI-1 degradation. The degradation of PAI-1 by P. gingivalis induced a delayed wound healing response in endothelial cell layers via the low-density lipoprotein receptor-related protein. Our results collectively suggested that the proteolysis of PAI-1 in endothelial cells by gingipains of P. gingivalis might lead to the deregulation of endothelial homeostasis, thereby contributing to the permeabilization and dysfunction of the vascular endothelial barrier.

  32. PPARγ-Induced Global H3K27 Acetylation Maintains Osteo/Cementogenic Abilities of Periodontal Ligament Fibroblasts. International-journal

    Hang Yuan, Shigeki Suzuki, Shizu Hirata-Tsuchiya, Akiko Sato, Eiji Nemoto, Masahiro Saito, Hideki Shiba, Satoru Yamada

    International journal of molecular sciences　22　(16)　2021/08/11

    DOI： 10.3390/ijms22168646 　

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    The periodontal ligament is a soft connective tissue embedded between the alveolar bone and cementum, the surface hard tissue of teeth. Periodontal ligament fibroblasts (PDLF) actively express osteo/cementogenic genes, which contribute to periodontal tissue homeostasis. However, the key factors maintaining the osteo/cementogenic abilities of PDLF remain unclear. We herein demonstrated that PPARγ was expressed by in vivo periodontal ligament tissue and its distribution pattern correlated with alkaline phosphate enzyme activity. The knockdown of PPARγ markedly reduced the osteo/cementogenic abilities of PDLF in vitro, whereas PPARγ agonists exerted the opposite effects. PPARγ was required to maintain the acetylation status of H3K9 and H3K27, active chromatin markers, and the supplementation of acetyl-CoA, a donor of histone acetylation, restored PPARγ knockdown-induced decreases in the osteo/cementogenic abilities of PDLF. An RNA-seq/ChIP-seq combined analysis identified four osteogenic transcripts, RUNX2, SULF2, RCAN2, and RGMA, in the PPARγ-dependent active chromatin region marked by H3K27ac. Furthermore, RUNX2-binding sites were selectively enriched in the PPARγ-dependent active chromatin region. Collectively, these results identified PPARγ as the key transcriptional factor maintaining the osteo/cementogenic abilities of PDLF and revealed that global H3K27ac modifications play a role in the comprehensive osteo/cementogenic transcriptional alterations mediated by PPARγ.

  33. 多孔性チタン膜間の細胞移動を利用した間葉系幹細胞の積層培養

    向阪 幸彦, 丸山 顕太郎, 石幡 浩志, 根本 英二, 佐々木 啓一, 山田 聡, 井上 拓, 千葉 茂樹, 初澤 毅

    生体医歯工学共同研究拠点成果報告書　令和2年度　73-73　2021/04

    Publisher: 東京医科歯科大学生体材料工学研究所

  34. DMP-1 promoter-associated antisense strand non-coding RNA, panRNA-DMP-1, physically associates with EGFR to repress EGF-induced squamous cell carcinoma migration

    Shigeki Suzuki, Hang Yuan, Shizu Hirata-Tsuchiya, Kazuma Yoshida, Akiko Sato, Eiji Nemoto, Hideki Shiba, Satoru Yamada

    Molecular and Cellular Biochemistry　2021/01/09

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1007/s11010-020-04046-5 　

    ISSN： 0300-8177

    eISSN： 1573-4919

  35. A large-scale observational study to investigate the current status of diabetic complications and their prevention in Japan (JDCP study 6): baseline dental and oral findings.

    Koji Inagaki, Takeshi Kikuchi, Toshihide Noguchi, Akio Mitani, Keiko Naruse, Tatsuaki Matsubara, Masamitsu Kawanami, Jun Negishi, Yasushi Furuichi, Eiji Nemoto, Satoru Yamada, Hiromasa Yoshie, Koichi Tabeta, Sachiyo Tomita, Atsushi Saito, Sayaka Katagiri, Yuichi Izumi, Hiroshi Nitta, Takanori Iwata, Yukihiro Numabe, Matsuo Yamamoto, Nobuo Yoshinari, Tsuyoshi Fujita, Hidemi Kurihara, Fusanori Nishimura, Toshihiko Nagata, Hiromichi Yumoto, Toru Naito, Kazuyuki Noguchi, Koichi Ito, Shinya Murakami, Rimei Nishimura, Naoko Tajima

    Diabetology international　12　(1)　52-61　2021/01

    DOI： 10.1007/s13340-020-00465-3 　

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    Japan Diabetes Complication and Prevention prospective (JDCP) study was conducted to examine the association between glycemic control and oral conditions in a large database of Japanese patients with diabetes. It included a total of 6099 patients with diabetes (range, 40-75 years) who had been treated as outpatients between 2007 and 2009. The mean number of present teeth at baseline was 19.8 and women with type 2 diabetes had fewer teeth than men with type 2 diabetes. Within the previous year, 17% of all patients had lost teeth. At baseline, 32% had experienced gingival swelling, 69% had brushed more than twice a day, 37% had used interdental cleaning aids, and 43% had undergone regular dental checkups. Multiple logistic regression analysis indicated that type 1 patients with HbA1c ≥ 7.0% were at higher risk of having fewer than 20 teeth (odds ratio [OR] 2.38; 95% confidence interval [CI] 1.25-4.78), and type 2 patients with HbA1c ≥ 8.0% also were at high risk of having fewer than 20 teeth (OR 1.16; 95% CI 1.00-1.34), after adjustment for nine possible confounding factors. In conclusion, patients with diabetes were found to be at high risk of tooth loss, and the poorer the glycemic control, the higher the risk of tooth loss in these patients.

  36. Evaluation of Preosteoblast MC3T3-E1 Cells Cultured on a Microporous Titanium Membrane Fabricated Using a Precise Mechanical Punching Process International-journal

    Jingyu Zhang, Yukihiko Sakisaka, Hiroshi Ishihata, Kentaro Maruyama, Eiji Nemoto, Shigeki Chiba, Masaru Nagamine, Hiroshi Hasegawa, Satoru Yamada

    Materials　13　(22)　5288-5288　2020/11/22

    Publisher: MDPI AG

    DOI： 10.3390/ma13225288 　

    eISSN： 1996-1944

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    The surface topography of Titanium (Ti) combined toughness and biocompatibility affects the attachment and migration of cells. Limited information of morphological characteristics, formed by precise machining in micron order, is currently available on the Ti that could promote osteoconduction. In the present study, a pure Ti membrane was pierced with precise 25 μm square holes at 75 μm intervals and appear burrs at the edge of aperture. We defined the surface without burrs as the “Head side” and that with burrs as the “Tail side”. The effects of the machining microtopography on the proliferation and differentiation of the preosteoblasts (MC3T3-E1 cells) were investigated. The cells were more likely to migrate to, and accumulate in, the aperture of holes on the head side, but grew uniformly regardless of holes on the tail side. The topography on the both surfaces increased osteopontin gene expression levels. Osteocalcin expression levels were higher on the head side than one on the blank scaffold and tail side (p &lt; 0.05). The osteocalcin protein expression levels were higher on the tail side than on the head side after 21 days of cultivation, and were comparable to the proportion of the calcified area (p &lt; 0.05). These results demonstrate the capacity of a novel microporous Ti membrane fabricated using a precise mechanical punching process to promote cell proliferation and activity.

  37. Effects of adjunctive probiotic L. reuteri lozenges on S/RSD outcomes at molar sites with deep pockets. International-journal Peer-reviewed

    Georgios Pelekos, Aneesha Acharya, Nemoto Eiji, Guang Hong, Wai Keung Leung, Colman McGrath

    Journal of clinical periodontology　47　(9)　1098-1107　2020/06/08

    DOI： 10.1111/jcpe.13329 　

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    AIM: To evaluate effects of probiotic Lactobacillus reuteri (L. reuteri) lozenges as an S/RSD adjunct on site-level changes at molars with deep pockets. MATERIALS AND METHODS: 447 molar sites with pockets ≥ 5 mm from a previous randomized clinical trial of adjunctive L. reuteri lozenges for 28 days were analyzed. Multilevel mixed-effect models (MLM) were constructed to analyze site-level outcomes "change in CAL" and "pocket closure" (residual PPD < 5 mm) in placebo and probiotic groups at 90 and 180 days. Possible patient-, tooth-, and site-level predictors were analyzed as fixed-effects. RESULTS: Estimated change in CAL in probiotic (90 day: 0.87 mm, 180 day: 0.68 mm) was greater than placebo treated molar sites (90 day: 0.73 mm, 180 day: 0.66 mm) and the relative risk (RR) of pocket closure in the probiotic group (90 day: 1.7, 180 day: 1.6) was higher as compared to placebo. Furcation involvement and BOP at site predicted significantly worse treatment outcomes. CONCLUSION: As compared to S/RSD with placebo, a 28-day course of adjunctive probiotic L. reuteri lozenges improved CAL change at molar sites with ≥ 5 mm deep pockets and conferred a higher probability of shallow residual pocket depth. Presence of furcation-involvement and bleeding on probing worsened treatment outcomes.

  38. メカノレスポンス因子MAP4K4の歯根膜における発現とその機能解析

    佐藤 瞭子, 鈴木 茂樹, 袁 航, 山本 真豊, 根本 英二, 齋藤 正寛, 山田 聡

    日本歯周病学会会誌　62　(春季特別)　129-129　2020/05

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

    eISSN： 1880-408X

  39. 炎症・メカニカル環境下における歯根膜細胞の新たな抗炎症システム マクロファージIL-10分泌誘導因子の発現

    佐藤 令, 丸山 顕太郎, 向阪 幸彦, 根本 英二, 鈴木 茂樹, 山田 聡

    日本歯周病学会会誌　62　(春季特別)　144-144　2020/05

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

    eISSN： 1880-408X

  40. 多孔性チタンメンブレンの表面性状による骨分化誘導能の評価

    向阪 幸彦, 丸山 顕太郎, 張井 玉, 石幡 浩志, 根本 英二, 佐々木 啓一, 山田 聡, 井上 拓, 千葉 茂樹, 初澤 毅

    生体医歯工学共同研究拠点成果報告書　令和元年度　132-132　2020/04

    Publisher: 東京医科歯科大学生体材料工学研究所

  41. 糖尿病合併症の実態とその抑制に関する大規模観察研究ベースライン時の口腔所見JDCP study 6

    稲垣 幸司, 菊池 毅, 野口 俊英, 三谷 章雄, 成瀬 桂子, 松原 達昭, 川浪 雅光, 根岸 淳, 古市 保志, 根本 英二, 山田 聡, 吉江 弘正, 多部田 康一, 富田 幸代, 齋藤 淳, 片桐 さやか, 和泉 雄一, 新田 浩, 岩田 隆紀, 沼部 幸博, 山本 松男, 吉成 伸夫, 藤田 剛, 栗原 英見, 西村 英紀, 永田 俊彦, 湯本 浩通, 内藤 徹, 野口 和行, 伊藤 公一, 村上 伸也, 西村 理明, 田嶼 尚子, 糖尿病データベース構築委員会

    糖尿病　63　(4)　195-205　2020/04

    Publisher: (一社)日本糖尿病学会

    ISSN： 0021-437X

    eISSN： 1881-588X

  42. A large-scale observational study to investigate the current status of diabetic complications and their prevention in Japan: Oral and dental findings at baseline -JDCP study 6- Peer-reviewed

    Koji Inagaki, Takeshi Kikuchi, Toshihide Noguchi, Akio Mitani, Keiko Naruse, Tatsuaki Matsubara, Masamitsu Kawanami, Jun Negishi, Yasushi Furuichi, Eiji Nemoto, Satoru Yamada, Hiromasa Yoshie, Koichi Tabeta, Sachiyo Tomita, Atsushi Saito, Sayaka Katagiri, Yuichi Izumi, Hiroshi Nitta, Takanori Iwata, Yukihiro Numabe, Matsuo Yamamoto, Nobuo Yoshinari, Tsuyoshi Fujita, Hidemi Kurihara, Fusanori Nishimura, Toshihiko Nagata, Hiromichi Yumoto, Toru Naito, Kazuyuki Noguchi, Koichi Ito, Shinya Murakami, Rimei Nishimura, Naoko Tajima

    Journal of the Japan Diabetes Society　63　(4)　195-205　2020

    DOI： 10.11213/tonyobyo.63.195 　

    ISSN： 0021-437X

  43. Cyclic Stretch Force Induces Periodontal Ligament Cells to Secrete Exosomes That Suppress IL-1β Production Through the Inhibition of the NF-κB Signaling Pathway in Macrophages. International-journal Peer-reviewed

    Zhuyu Wang, Kentarou Maruyama, Yukihiko Sakisaka, Shigeki Suzuki, Hiroyuki Tada, Mizuki Suto, Masahiro Saito, Satoru Yamada, Eiji Nemoto

    Frontiers in immunology　10　1310-1310　2019

    DOI： 10.3389/fimmu.2019.01310 　

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    In the oral mechanical environment, periodontal ligament cells (PDL cells) contribute to maintaining periodontal tissue homeostasis. Recent studies showed that exosomes, which are small vesicles secreted by various types of cells, play a pivotal role in cell-to-cell communication in biological processes. We examined the secretion of exosomes from PDL cells stimulated with cyclic stretch and their role in the inflammatory response of macrophages using the human macrophage cell line THP-1 and human primary monocytes/macrophages. We prepared supernatants from human PDL cells (PDL-sup) stimulated with cyclic stretch. The treatment of macrophages with PDL-sup, but not PDL-sup from unstimulated PDL cells, inhibited the production of IL-1β in LPS/nigericin-stimulated macrophages. The pretreatment of PDL cells with GW4869, an inhibitor of exosome secretion, or siRNA for Rab27B, which controls exosome secretion, abrogated the inhibitory effects of PDL-sup. A transmission electron microscopy analysis demonstrated the existence of exosomes with diameters ranging between 30 and 100 nm in PDL-sup, suggesting that exosomes in PDL-sup contribute to this inhibition. An immunofluorescence microscopy analysis revealed that exosomes labeled with PKH67, a fluorescent dye, were incorporated by macrophages as early as 2 h after the addition of exosomes. Purified exosomes inhibited IL-1β production in LPS/nigericin-stimulated macrophages and the nuclear translocation of NF-κB as well as NF-κB p65 DNA-binding activity in LPS-stimulated macrophages, suggesting that exosomes suppress IL-1β production by inhibiting the NF-κB signaling pathway. Our results indicate that PDL cells in mechanical environments contribute to the maintenance of periodontal immune/inflammatory homeostasis by releasing exosomes.

  44. Periodontal Regeneration by Allogeneic Transplantation of Adipose Tissue Derived Multi-Lineage Progenitor Stem Cells in vivo. International-journal Peer-reviewed

    Venkataiah, VS, K. Handa, MM. Njuguna, T. Hasegawa, K. Maruyama, E. Nemoto, S. Yamada, S. Sugawara, L. Lu, M. Takedachi, S. Murakami, H. Okura, A. Matsuyama, M

    Sci Rep.　29　(9)　921-921　2019/01

    DOI： 10.1038/s41598-018-37528-0 　

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    The ultimate goal of periodontal disease treatment is the reorganization of functional tissue that can regenerate lost periodontal tissue. Regeneration of periodontal tissues is clinically possible by using autogenic transplantation of MSCs. However, autologous MSC transplantation is limited depending on age, systemic disease and tissue quality, thus precluding their clinical application. Therefore, we evaluated the efficacy of allogeneic transplantation of adipose-derived multi-lineage progenitor cells (ADMPC) in a micro-mini pig periodontal defect model. ADMPC were isolated from the greater omentum of micro-mini pigs, and flow cytometry analysis confirmed that the ADMPC expressed MSC markers, including CD44 and CD73. ADMPC exhibited osteogenic, adipogenic and periodontal ligament differentiation capacities in differentiation medium. ADMPC showed high expression of the immune suppressive factors GBP4 and IL1-RA upon treatment with a cytokine cocktail containing interferon-γ, tumor necrosis factor-α and interleukin-6. Allogeneic transplantation of ADMPC in a micro-mini pig periodontal defect model showed significant bone regeneration ability based on bone-morphometric analysis. Moreover, the regeneration ability of ADMPC by allogeneic transplantation was comparable to those of autologous transplantation by histological analysis. These results indicate that ADMPC have immune-modulation capability that can induce periodontal tissue regeneration by allogeneic transplantation.

  45. Mechanical regulation of macrophage function – cyclic tensile force inhibits NLRP3 inflammasome-dependent IL-1β secretion in murine macrophages. International-journal Peer-reviewed

    Maruyama, K, E. Nemoto, S. Yamada

    Inflamm. Regen.　39　3-3　2019

    DOI： 10.1186/s41232-019-0092-2 　

    ISSN： 1880-9693

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    Mechanical stress maintains tissue homeostasis by regulating many cellular functions including cell proliferation, differentiation, and inflammation and immune responses. In inflammatory microenvironments, macrophages in mechanosensitive tissues receive mechanical signals that regulate various cellular functions and inflammatory responses. Macrophage function is affected by several types of mechanical stress, but the mechanisms by which mechanical signals influence macrophage function in inflammation, such as the regulation of interleukin-1β by inflammasomes, remain unclear. In this review, we describe the role of mechanical stress in macrophage and monocyte cell function.

  46. Cyclic stretch negatively regulates IL-1β secretion through the inhibition of NLRP3 inflammasome activation by attenuating the AMP kinase pathway Peer-reviewed

    Kentaro Maruyama, Yukihiko Sakisaka, Mizuki Suto, Hiroyuki Tada, Takashi Nakamura, Satoru Yamada, Eiji Nemoto

    Frontiers in Physiology　9　(JUN)　802　2018/06/28

    DOI： 10.3389/fphys.2018.00802 　

    eISSN： 1664-042X

  47. Extracellular calcium increases fibroblast growth factor 2 gene expression via extracellular signal-regulated kinase 1/2 and protein kinase A signaling in mouse dental papilla cells. International-journal Peer-reviewed

    Kanaya S, Xiao B, Sakisaka Y, Suto M, Maruyama K, Saito M, Nemoto E

    Journal of applied oral science : revista FOB　26　e20170231　2018/05

    DOI： 10.1590/1678-7757-2017-0231 　

    ISSN： 1678-7757

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    We previously reported that elevated extracellular calcium (Ca2+) levels increase bone morphogenetic protein 2 expression in human dental pulp (hDP) cells. However, it is unknown whether extracellular Ca2+ affects the expression of other growth factors such as fibroblast growth factor 2 (FGF2). The present study aimed to examine the effect of extracellular Ca2+ on FGF2 gene expression in hDP and immortalized mouse dental papilla (mDP) cells. Cells were stimulated with 10 mM CaCl2 in the presence or absence of cell signaling inhibitors. FGF2 gene expression was assessed using real-time polymerase chain reaction. The phosphorylation status of signaling molecules was examined by Western blotting. Extracellular Ca2+ increased FGF2 gene expression in mDP and hDP cells. Gene expression of the calcium-sensing receptor and G protein-coupled receptor family C group 6 member A, both of which are extracellular Ca2+ sensors, was not detected. Ca2+-mediated Fgf2 expression was reduced by pretreatment with the protein kinase A (PKA) inhibitor H-89 or extracellular signal-regulated kinase (ERK) 1/2 inhibitor PD98059 but not by pretreatment with the protein kinase C inhibitor GF-109203X or p38 inhibitor SB203580. Extracellular Ca2+ increased PKA activity and ERK1/2 phosphorylation. Ca2+-induced PKA activity decreased by pretreatment with PD98059. These findings indicate that elevated extracellular Ca2+ levels led to increased Fgf2 expression through ERK1/2 and PKA in mDP cells and that this mechanism may be useful for designing regenerative therapies for dentin.

  48. ヒト歯根膜細胞の分化・増殖に対するBerberineの作用 Peer-reviewed

    池野 修功, 根本 英二, 金谷 聡介, 須藤 瑞樹, 向阪 幸彦, 島内 英俊, 山田 聡

    日本歯周病学会会誌　60　(1)　13-25　2018/03

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

    eISSN： 1880-408X

  49. 偏心モーター内蔵型振動スケーラーの歯石除去における臨床的有効性の評価 Peer-reviewed

    丸山顕太郎, 池野修功, 小松秀裕, 向阪幸彦, 大方広志, 須藤瑞樹, 根本英二, 庄司茂

    日歯保存誌　60　(3)　111-119　2017

  50. Increases in IL-33 production by fimbriae and lipopeptide from Porphyromonas gingivalis in mouse bone marrow-derived dendritic cells via Toll-like receptor 2 Peer-reviewed

    Hiroyuki Tada, Risako Suzuki, Eiji Nemoto, Hidetoshi Shimauchi, Kenji Matsushita, Haruhiko Takada

    BIOMEDICAL RESEARCH-TOKYO　38　(3)　189-195　2017

    DOI： 10.2220/biomedres.38.189 　

    ISSN： 0388-6107

    eISSN： 1880-313X

  51. Role of the Wnt signaling molecules in the tooth Peer-reviewed

    Masato Tamura, Eiji Nemoto

    Japanese Dental Science Review　52　(4)　75-83　2016/11/01

    Publisher: Elsevier Ltd

    DOI： 10.1016/j.jdsr.2016.04.001 　

    ISSN： 2213-6851 1882-7616

  52. Metabotropic glutamate receptor 1 promotes cementoblast proliferation via MAP kinase signaling pathways Peer-reviewed

    Sousuke Kanaya, Hidehiro Komatsu, Hidetoshi Shimauchi, Eiji Nemoto

    CONNECTIVE TISSUE RESEARCH　57　(5)　417-426　2016/09

    DOI： 10.1080/03008207.2016.1195826 　

    ISSN： 0300-8207

    eISSN： 1607-8438

  53. p38 MAP kinase is required for Wnt3a-mediated osterix expression independently of Wnt-LRP5/6-GSK3 beta signaling axis in dental follicle cells Peer-reviewed

    Yukihiko Sakisaka, Sousuke Kanaya, Takashi Nakamura, Masato Tamura, Hidetoshi Shimauchi, Eiji Nemoto

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　478　(2)　527-532　2016/09

    DOI： 10.1016/j.bbrc.2016.07.076 　

    ISSN： 0006-291X

    eISSN： 1090-2104

  54. Modulation of stromal cell-derived factor 1 alpha (SDF-1 alpha) and its receptor CXCR4 in Porphyromonas gingivalis-induced periodontal inflammation Peer-reviewed

    Jiang Sun, Eiji Nemoto, Guang Hong, Keiichi Sasaki

    BMC ORAL HEALTH　17　(1)　26　2016/07

    DOI： 10.1186/s12903-016-0250-8 　

    ISSN： 1472-6831

  55. Wnt3a signaling induces murine dental follicle cells to differentiate into cementoblastic/osteoblastic cells via an osterix-dependent pathway Peer-reviewed

    E. Nemoto, Y. Sakisaka, M. Tsuchiya, M. Tamura, T. Nakamura, S. Kanaya, M. Shimonishi, H. Shimauchi

    JOURNAL OF PERIODONTAL RESEARCH　51　(2)　164-174　2016/04

    DOI： 10.1111/jre.12294 　

    ISSN： 0022-3484

    eISSN： 1600-0765

  56. 歯周組織におけるWntシグナルの役割 Peer-reviewed

    根本 英二

    日歯周誌　58　(1)　16-24　2016

  57. Periodontal Disease Is Associated with Insomnia among Victims of the Great East Japan Earthquake: A Panel Study Initiated Three Months after the Disaster Peer-reviewed

    Masahiro Tsuchiya, Jun Aida, Yoshihiro Hagiwara, Yumi Sugawara, Yasutake Tomata, Mari Sato, Takashi Watanabe, Hiroaki Tomita, Eiji Nemoto, Makoto Watanabe, Ken Osaka, Ichiro Tsuji

    TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE　237　(2)　83-90　2015/10

    DOI： 10.1620/tjem.237.83 　

    ISSN： 0040-8727

    eISSN： 1349-3329

  58. Wnt5a attenuates Wnt3a-induced alkaline phosphatase expression in dental follicle cells Peer-reviewed

    Yukihiko Sakisaka, Masahiro Tsuchiya, Takashi Nakamura, Masato Tamura, Hidetoshi Shimauchi, Eiji Nemoto

    EXPERIMENTAL CELL RESEARCH　336　(1)　85-93　2015/08

    DOI： 10.1016/j.yexcr.2015.06.013 　

    ISSN： 0014-4827

    eISSN： 1090-2422

  59. Calcium Phosphate Particles Induce Interleukin-8 Expression in a Human Gingival Epithelial Cell Line via the Nuclear Factor-kappa B Signaling Pathway Peer-reviewed

    Yu Sakai, Eiji Nemoto, Sousuke Kanaya, Mitsuru Shimonishi, Hidetoshi Shimauchi

    JOURNAL OF PERIODONTOLOGY　85　(10)　1464-1473　2014/10

    DOI： 10.1902/jop.2014.130709 　

    ISSN： 0022-3492

    eISSN： 1943-3670

  60. Cyclic tensile force up-regulates BMP-2 expression through MAP kinase and COX-2/PGE(2) signaling pathways in human periodontal ligament cells Peer-reviewed

    Risako Suzuki, Eiji Nemoto, Hidetoshi Shimauchi

    EXPERIMENTAL CELL RESEARCH　323　(1)　232-241　2014/04

    DOI： 10.1016/j.yexcr.2014.02.013 　

    ISSN： 0014-4827

    eISSN： 1090-2422

  61. Extracellular ATP inhibits IL-1-induced MMP-1 expression through the action of CD39/nucleotidase triphosphate dephosphorylase-1 on human gingival fibroblasts Peer-reviewed

    Eiji Nemoto, Kazuhiro Gotoh, Masahiro Tsuchiya, Yukihiko Sakisaka, Hidetoshi Shimauchi

    INTERNATIONAL IMMUNOPHARMACOLOGY　17　(3)　513-518　2013/11

    DOI： 10.1016/j.intimp.2013.07.014 　

    ISSN： 1567-5769

    eISSN： 1878-1705

  62. Calcium-mediated increased expression of fibroblast growth factor-2 acts through NF-kappa B and PGE(2)/EP4 receptor signaling pathways in cementoblasts Peer-reviewed

    Sousuke Kanaya, Eiji Nemoto, Yukihiko Sakisaka, Hidetoshi Shimauchi

    BONE　56　(2)　398-405　2013/10

    DOI： 10.1016/j.bone.2013.06.031 　

    ISSN： 8756-3282

  63. Molecular mechanism of differentiation of the tooth and periodontium-related cells : Approach to oral regenerative medicine

    NEMOTO Eiji

    JOURNAL OF THE JAPANESE ORGANISATION FOR RESEARCH OF PERIODONTOLOGY　55　(3)　239-248　2013/09/02

    Publisher: JAPANESE SOCIETY OF PERIODONTOLOGY

    DOI： 10.2329/perio.55.239 　

    ISSN： 0385-0110

  64. Nanohydroxyapatite increases BMP-2 expression via a p38 MAP kinase dependent pathway in periodontal ligament cells Peer-reviewed

    Mizuki Suto, Eiji Nemoto, Sousuke Kanaya, Risako Suzuki, Masahiro Tsuchiya, Hidetoshi Shimauchi

    ARCHIVES OF ORAL BIOLOGY　58　(8)　1021-1028　2013/08

    DOI： 10.1016/j.archoralbio.2013.02.014 　

    ISSN： 0003-9969

  65. 口腔再生医学の確立を目指した歯・歯周組織関連細胞の分化制御の分子機構 Peer-reviewed

    根本 英二

    日歯周誌　58　(1)　16-24　2013

  66. Extracellular beta-NAD(+) Inhibits Interleukin-1-Induced Matrix Metalloproteinase-1 and-3 Expression on Human Gingival Fibroblasts Peer-reviewed

    Kazuhiro Gotoh, Eiji Nemoto, Sousuke Kanaya, Hidetoshi Shimauchi

    CONNECTIVE TISSUE RESEARCH　54　(3)　204-209　2013

    DOI： 10.3109/03008207.2013.782013 　

    ISSN： 0300-8207

  67. Wnt5a signaling is a substantial constituent in bone morphogenetic protein-2-mediated osteoblastogenesis Peer-reviewed

    Eiji Nemoto, Yukari Ebe, Sousuke Kanaya, Masahiro Tsuchiya, Takashi Nakamura, Masato Tamura, Hidetoshi Shimauchi

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　422　(4)　627-632　2012/06

    DOI： 10.1016/j.bbrc.2012.05.039 　

    ISSN： 0006-291X

  68. Interleukin-6 Maintains Glucose Homeostasis to Support Strenuous Masseter Muscle Activity in Mice Peer-reviewed

    Masahiro Tsuchiya, Tomomi Kiyama, Shinobu Tsuchiya, Hirohisa Takano, Eiji Nemoto, Keiichi Sasaki, Makoto Watanabe, Shunji Sugawara, Yasuo Endo

    TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE　227　(2)　109-117　2012/06

    DOI： 10.1620/tjem.227.109 　

    ISSN： 0040-8727

    eISSN： 1349-3329

  69. Extracellular phosphate increases bone morphogenetic protein-2 expression in human dental pulp cells and human periodontal ligament cells Peer-reviewed

    Eiji Nemoto, Hiroyuki Tada, Hidetoshi Shimauchi

    Interface Oral Health Science 2011　143-144　2012/01/01

    Publisher: Springer Japan

    DOI： 10.1007/978-4-431-54070-0_35 　

  70. Phosphate increases bone morphogenetic protein-2 expression through cAMP-dependent protein kinase and ERK1/2 pathways in human dental pulp cells Peer-reviewed

    Hiroyuki Tada, Eiji Nemoto, Brian L. Foster, Martha J. Somerman, Hidetoshi Shimauchi

    BONE　48　(6)　1409-1416　2011/06

    DOI： 10.1016/j.bone.2011.03.675 　

    ISSN： 8756-3282

  71. Elevated extracellular calcium increases fibroblast growth factor-2 gene and protein expression levels via a cAMP/PKA dependent pathway in cementoblasts Peer-reviewed

    Sousuke Kanaya, Eiji Nemoto, Yukari Ebe, Martha J. Somerman, Hidetoshi Shimauchi

    BONE　47　(3)　564-572　2010/09

    DOI： 10.1016/j.bone.2010.05.042 　

    ISSN： 8756-3282

  72. Elevated extracellular calcium increases expression of bone morphogenetic protein-2 gene via a calcium channel and ERK pathway in human dental pulp cells Peer-reviewed

    Hiroyuki Tada, Eiji Nemoto, Sousuke Kanaya, Nozomu Hamaji, Hisae Sato, Hidetoshi Shimauchi

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　394　(4)　1093-1097　2010/04

    DOI： 10.1016/j.bbrc.2010.03.135 　

    ISSN： 0006-291X

  73. Role of the Wnt signaling pathway in bone and tooth Peer-reviewed

    Masato Tamura, Eiji Nemoto, Mari M. Sato, Aiko Nakashima, Hidetoshi Shimauchi

    Frontiers in Bioscience - Elite　2　(4)　1405-1413　2010/01/06

    ISSN： 1945-0494 1945-0508

  74. Proliferation of periodontal ligament cells on biodegradable honeycomb film scaffold with unified micropore organization Peer-reviewed

    Ishihata H, Tanaka M, Iwama N, Ara M, Shimonishi M, Nagamine M, Murakami N, Kanaya S, Nemoto E, Shimauchi H, Shimomura M

    Journal of Biomechanical Science and Engineering　5　(3)　252-261　2010

    Publisher: The Japan Society of Mechanical Engineers

    DOI： 10.1299/jbse.5.252 　

    ISSN： 1880-9863

  75. Porphyromonas gingivalis fimbriae induce unique dendritic cell subsets via Toll-like receptor 2 Peer-reviewed

    S. Kanaya, E. Nemoto, T. Ogawa, H. Shimauchi

    JOURNAL OF PERIODONTAL RESEARCH　44　(4)　543-549　2009/08

    DOI： 10.1111/j.1600-0765.2008.01149.x 　

    ISSN： 0022-3484

  76. Wnt signaling inhibits cementoblast differentiation and promotes proliferation Peer-reviewed

    Eiji Nemoto, Yohei Koshikawa, Sousuke Kanaya, Masahiro Tsuchiya, Masato Tamura, Martha J. Somerman, Hidetoshi Shimauchi

    BONE　44　(5)　805-812　2009/05

    DOI： 10.1016/j.bone.2008.12.029 　

    ISSN： 8756-3282

  77. Control of human periodontal ligament cells proliferation on honeycomb-patterned films for regenerative periodontal therapy Peer-reviewed

    Iwama N, Tanaka M, Ishihata H, Ara M, Shimonishi M, Nagamine M, Murakami N, Kanaya S, Nemoto E, Shimauchi H, Shimomura M

    European Cells and Materials　18　(SUPPL. 2)　67　2009

  78. Expression of functional Toll-like receptors and nucleotide-binding oligomerization domain proteins in murine cementoblasts and their upregulation during cell differentiation Peer-reviewed

    E. Nemoto, T. Honda, S. Kanaya, H. Takada, H. Shimauchi

    JOURNAL OF PERIODONTAL RESEARCH　43　(5)　585-593　2008/10

    DOI： 10.1111/j.1600-0765.2008.01096.x 　

    ISSN： 0022-3484

  79. Induction of fibroblast growth factor 2 mRNA by extracellular Ca2+ in mouse cementoblast

    Kanaya Sousuke, Nemoto Eiji, Shimauchi Hidetoshi

    Program and Abstracts of Annual Meeting of the Japanese Society of Periodontology　2008　68-68　2008

    Publisher: JAPANESE SOCIETY OF PERIODONTOLOGY

    DOI： 10.14833/amjsp.2008s.0.68.0 　

  80. Regulation of cementoblast function by P. gingivalis lipopolysaccharide via TLR2 Peer-reviewed

    E. Nemoto, R. P. Darveau, B. L. Foster, G. R. Nogueira-Filho, M. J. Somerman

    JOURNAL OF DENTAL RESEARCH　85　(8)　733-738　2006/08

    DOI： 10.1177/154405910608500809 　

    ISSN： 0022-0345

  81. Retinoic acid is a potential negative regulator for differentiation of human periodontal ligament cells Peer-reviewed

    N Shibuya, E Nemoto, S Kanaya, R Kunii, H Shimauchi

    JOURNAL OF PERIODONTAL RESEARCH　40　(6)　432-440　2005/12

    DOI： 10.1111/j.1600-0765.2005.00811.x 　

    ISSN： 0022-3484

  82. Porphyromonas gingivalis fimbriae induce CD14+CD16+ dendritic cell phenotype via TLR2 Peer-reviewed

    S. Kanaya, E. Nemoto, T. Ogawa, M. Minamibuchi, T. Honda, H. Shimauchi

    International Congress Series　1284　169-174　2005/09

    DOI： 10.1016/j.ics.2005.06.034 　

    ISSN： 0531-5131

  83. Cleavage of PDGF receptor on periodontal ligament cells by elastase Peer-reviewed

    E Nemoto, S Kanaya, M Minamibuchi, H Shimauchi

    JOURNAL OF DENTAL RESEARCH　84　(7)　629-633　2005/07

    DOI： 10.1177/154405910508400709 　

    ISSN： 0022-0345

  84. Expression of CD13/aminopeptidase N on human gingival fibroblasts and up-regulation upon stimulation with interleukin-4 and interleukin-13 Peer-reviewed

    R Kunii, E Nemoto, S Kanaya, T Tsubahara, H Shimauchi

    JOURNAL OF PERIODONTAL RESEARCH　40　(2)　138-146　2005/04

    DOI： 10.1111/j.1600-0765.2004.00778.x 　

    ISSN： 0022-3484

  85. The involvement of platelet-derived growth factor receptors and insulin-like growth factor-I receptors signaling during mineralized nodule formation by human periodontal ligament cells. Peer-reviewed

    Nemoto Eiji, Shimonishi Mitsuru, Nitta Yasutaka, Shimauchi Hidetoshi

    J Periodontal Res　39　(6)　388-397　2004/12

    DOI： 10.1111/j.1600-0765.2004.00750.x 　

    ISSN： 0022-3484

  86. Porphyromonas gingivalis lipopolysaccharides induce maturation of dendritic cells with CD14+CD16+ phenotype. Peer-reviewed

    Kanaya Sousuke, Nemoto Eiji, Ogawa Tomohiko, Shimauchi Hidetoshi

    Eur J Immunol　34　(5)　1451-1460　2004/05

    DOI： 10.1002/eji.200324549 　

    ISSN： 0014-2980

  87. Expression of CD73/ecto-5 '-nucleotidase on human gingival fibroblasts and contribution to the inhibition of interleukin-1 alpha-induced granulocyte-macrophage colony stimulating factor production Peer-reviewed

    E Nemoto, R Kunii, H Tada, T Tsubahara, H Ishihata, H Shimauchi

    JOURNAL OF PERIODONTAL RESEARCH　39　(1)　10-19　2004/02

    ISSN： 0022-3484

  88. Proteolysis of ICAM-1 on human oral epithelial cells by gingipains Peer-reviewed

    H Tada, S Sugawara, E Nemoto, T Imamura, J Potempa, J Travis, H Shimauchi, H Takada

    JOURNAL OF DENTAL RESEARCH　82　(10)　796-801　2003/10

    ISSN： 0022-0345

  89. ヒト歯肉線維芽細胞におけるNeutral endopeptidase 24.11(CD10) およ, びAminopeptidase N(CD13)の発現 ―インタ？ロイキン４による発現増強― Peer-reviewed

    鍔原泰介, 根本英二, 真柳弦, 島内英俊

    日本歯科保存学雑誌　46　(3)　425-434　2003/04

    ISSN： 0387-2343

  90. Porphyromonas gingivalisジンジパインはヒト歯肉線維芽細胞CD14を分解してLPS不応答性を誘導する

    多田 浩之, 菅原 俊二, 今村 隆寿, 島内 英俊, 高田 春比古, 根本 英二, 高橋 信博

    日本細菌学雑誌　58　(1)　158-158　2003/02

    Publisher: 日本細菌学会

    ISSN： 0021-4930

    eISSN： 1882-4110

  91. Disruption of CD40/CD40 ligand interaction with cleavage of CD40 on human gingival fibroblasts by human leukocyte elastase resulting in down-regulation of chemokine production Peer-reviewed

    E Nemoto, H Tada, H Shimauchi

    JOURNAL OF LEUKOCYTE BIOLOGY　72　(3)　538-545　2002/09

    ISSN： 0741-5400

  92. Expression of neutral endopeptidase 24.11 (CD10) and aminopeptidase N (CD13) on human gingival fibroblasts. Invited

    Nemoto E., T. Tsubahara, S. Kanaya, H. Shimauchi

    Dentistry in Japan　38　121-124　2002/08

  93. Proteolysis of CD14 on human gingival fibroblasts by arginine-specific cysteine proteinases from Porphyromonas gingivalis leading to down-regulation of lipopolysaccharide-induced interleukin-8 production Peer-reviewed

    H Tada, S Sugawara, E Nemoto, N Takahashi, T Imamura, J Potempa, J Travis, H Shimauchi, H Takada

    INFECTION AND IMMUNITY　70　(6)　3304-3307　2002/06

    DOI： 10.1128/IAI.70.6.3304-3307.2002 　

    ISSN： 0019-9567

  94. Saccharomyces cerevisiae- and Candida albicans-derived mannan induced production of tumor necrosis factor alpha by human monocytes in a CD14-and Toll-like receptor 4-dependent manner Peer-reviewed

    H Tada, E Nemoto, H Shimauchi, T Watanabe, T Mikami, T Matsumoto, N Ohno, H Tamura, K Shibata, S Akashi, K Miyake, S Sugawara, H Takada

    MICROBIOLOGY AND IMMUNOLOGY　46　(7)　503-512　2002

    DOI： 10.1111/j.1348-0421.2002.tb02727.x 　

    ISSN： 0385-5600

  95. ヒト歯肉線維芽細胞膜上のCD26/dipeptidyl peptidase IV —サイトカインおよび菌体成分による発現増強— Peer-reviewed

    根本英二, 菅原俊二, 高田春比古, 庄司 茂, 堀内 博

    日本炎症学会雑誌　20　(1)　13-20　2002

  96. 炎症反応における好中球エラスターゼの新たな機能 — CD14依存性IL-8産生の選択的抑制機構— Peer-reviewed

    根本英二, 島内英俊

    日本炎症学会雑誌　22　(1)　13-20　2002

  97. Cleavage of CD14 on human gingival fibroblasts cocultured with activated neutrophils is mediated by human leukocyte elastase resulting in down-regulation of lipopolysaccharide-induced IL-8 production Peer-reviewed

    E Nemoto, S Sugawara, H Tada, H Takada, H Shimauchi, H Horiuchi

    JOURNAL OF IMMUNOLOGY　165　(10)　5807-5813　2000/11

    ISSN： 0022-1767

  98. Proteolysis of human monocyte CD14 by cysteine proteinases (Gingipains) from Porphyromonas gingivalis leading to lipopolysaccharide hyporesponsiveness Peer-reviewed

    S Sugawara, E Nemoto, H Tada, K Miyake, T Imamura, H Takada

    JOURNAL OF IMMUNOLOGY　165　(1)　411-418　2000/07

    ISSN： 0022-1767

    eISSN： 1550-6606

  99. Increase of CD26/dipeptidyl peptidase IV expression on human gingival fibroblasts upon stimulation with cytokines and bacterial components Peer-reviewed

    E Nemoto, S Sugawara, H Takada, S Shoji, H Horiuchi

    INFECTION AND IMMUNITY　67　(12)　6225-6233　1999/12

    ISSN： 0019-9567

  100. Heterogeneous expression and release of CD14 by human gingival fibroblasts: Characterization and CD14-mediated interleukin-8 secretion in response to lipopolysaccharide Peer-reviewed

    S Sugawara, A Sugiyama, E Nemoto, H Rikiishi, H Takada

    INFECTION AND IMMUNITY　66　(7)　3043-3049　1998/07

    ISSN： 0019-9567

  101. Circulating promyelocytes and low levels of CD16 expression on polymorphonuclear leukocytes accompany early-onset periodontitis Peer-reviewed

    E Nemoto, M Nakamura, S Shoji, H Horiuchi

    INFECTION AND IMMUNITY　65　(9)　3906-3912　1997/09

    ISSN： 0019-9567

  102. Molecular cloning of a functional murine arginine-specific mono-ADP-ribosyltransferase and its expression in lymphoid cells Peer-reviewed

    YJ Yu, S Okamoto, E Nemoto, G Dennert

    DNA AND CELL BIOLOGY　16　(2)　235-244　1997/02

    ISSN： 1044-5498

  103. Regulation of cytotoxic T cell functions by a GPI-anchored ECTO-ADP-ribosyltransferase Peer-reviewed

    J Wang, E Nemoto, G Dennert

    ADP-RIBOSYLATION IN ANIMAL TISSUES　419　191-201　1997

    ISSN： 0065-2598

  104. Cell surface ADP-ribosyltransferase regulates lymphocyte function-associated molecule-1 (LFA-1) function in T cells. Peer-reviewed

    Nemoto E. Y. Yu, G. Dennert, G. Dennert

    J. Immunol.,　157　(8)　3341-3349　1996/08

  105. Regulation of CTL by ecto-nicotinamide adenine dinucleotide (NAD) involves ADP-ribosylation of a p56(lck)-associated protein Peer-reviewed

    J Wang, E Nemoto, G Dennert

    JOURNAL OF IMMUNOLOGY　156　(8)　2819-2827　1996/04

    ISSN： 0022-1767

  106. Release of a glycosylphosphatidylinositol-anchored ADP-ribosyltransferase from cytotoxic T cells upon activation Peer-reviewed

    E Nemoto, S Stohlman, G Dennert

    JOURNAL OF IMMUNOLOGY　156　(1)　85-92　1996/01

    ISSN： 0022-1767

    eISSN： 1550-6606

  107. Isolation of a new superantigen with a potent mitogenic activity to murine T cells from Streptococcus pyogenes Peer-reviewed

    Eiji Nemoto, Hidemi Rikiishi, Shunji Sugawara, Shigefumi Okamoto, Keiji Tamura, Yasuo Maruyama, Katsuo Kumagai

    FEMS Immunology and Medical Microbiology　15　(2-3)　81-91　1996

    Publisher: Blackwell Publishing Ltd

    DOI： 10.1016/0928-8244(96)00044-2 　

    ISSN： 0928-8244

  108. REGULATION OF CYTOTOXIC T-CELLS BY ECTO-NICOTINAMIDE ADENINE-DINUCLEOTIDE (NAD) CORRELATES WITH CELL-SURFACE GPI-ANCHORED/ARGININE ADP-RIBOSYLTRANSFERASE Peer-reviewed

    J WANG, E NEMOTO, AY KOTS, HR KASLOW, G DENNERT

    JOURNAL OF IMMUNOLOGY　153　(9)　4048-4058　1994/11

    ISSN： 0022-1767

  109. ELEVATED PRODUCTION OF INTERLEUKIN-6 BY HEPATIC MNC CORRELATES WITH ICAM-1 EXPRESSION ON THE HEPATIC SINUSOIDAL ENDOTHELIAL-CELLS IN AUTOIMMUNE MRL/LPR MICE Peer-reviewed

    T OHTEKI, S OKAMOTO, M NAKAMURA, E NEMOTO, K KUMAGAI

    IMMUNOLOGY LETTERS　36　(2)　145-152　1993/05

    ISSN： 0165-2478

Show all ︎Show first 5

Misc. 85

  1. Clinical evaluation of the ability of an electric root canal meter to detect lateral root canals based on a comparison with CBCT

    庄司茂, 庄司茂, 丸山顕太郎, 須藤圭一, 根本英二

    日本歯内療法学会雑誌　44　(3)　2023

    ISSN： 1347-8672

  2. Loss of IκBζ Drives Dentin Formation via Altered H3K4me3 Status

    H. Yuan, S. Suzuki, H. Terui, S. Hirata-Tsuchiya, E. Nemoto, K. Yamasaki, M. Saito, H. Shiba, S. Aiba, S. Yamada

    Journal of Dental Research　101　(8)　951-961　2022/02/22

    Publisher: SAGE Publications

    DOI： 10.1177/00220345221075968 　

    ISSN： 0022-0345

    eISSN： 1544-0591

  3. 歯根膜線維芽細胞の骨/セメント形成能を維持するためには、PPARγによるH3K27全体のアセチル化が必要である(PPARγ-induced global H3K27 acetylation is required to maintain osteo/cementogenic abilities of periodontal ligament fibroblasts)

    Hang Yuan, Suzuki Shigeki, Sato Akiko, Nemoto Eiji, Saito Masahiro, Shiba Hideki, Yamada Satoru

    日本歯周病学会会誌　63　(秋季特別)　124-124　2021/10

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

    eISSN： 1880-408X

  4. 周期的伸展刺激を受容したヒト歯根膜線維芽細胞はPGE2を介してM2マクロファージ分化を誘導する

    丸山 顕太郎, 佐藤 令, 向阪 幸彦, 鈴木 茂樹, 根本 英二, 山田 聡

    日本歯周病学会会誌　63　(秋季特別)　139-139　2021/10

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

    eISSN： 1880-408X

  5. 周期的伸展刺激を受容したヒト歯根膜線維芽細胞はPGE2を介してM2マクロファージ分化を誘導する

    丸山 顕太郎, 佐藤 令, 向阪 幸彦, 鈴木 茂樹, 根本 英二, 山田 聡

    日本歯周病学会会誌　63　(秋季特別)　139-139　2021/10

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

    eISSN： 1880-408X

  6. 多孔性チタン膜間の細胞移動を利用した間葉系幹細胞の積層培養

    向阪 幸彦, 丸山 顕太郎, 石幡 浩志, 根本 英二, 佐々木 啓一, 山田 聡, 井上 拓, 千葉 茂樹, 初澤 毅

    生体医歯工学共同研究拠点成果報告書　令和2年度　73-73　2021/04

    Publisher: 東京医科歯科大学生体材料工学研究所

  7. 周期的伸展刺激を受容したヒト歯根膜線維芽細胞はPGE2を介してM2マクロファージ分化を誘導する

    丸山顕太郎, 佐藤令, 向阪幸彦, 鈴木茂樹, 根本英二, 山田聡

    日本歯周病学会会誌(Web)　63　2021

    ISSN： 1880-408X

  8. - Peer-reviewed

    H. Yuan, S. Suzuki, A. Sato, T. Yamamoto, E. Nemoto, M. Saito, S. Yamada

    94　2020/11

  9. 広汎性重度慢性歯周炎患者に対し非外科による特異的抗菌療法と歯周矯正、歯周補綴により包括的治療を行った一症例 Peer-reviewed

    白石大祐, 根本英二, 山田聡

    日本歯周病学会誌秋季特別号　62　(秋季特別)　132-132　2020/10

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

    eISSN： 1880-408X

  10. PPGAγは歯周靱帯細胞の硬部組織形成細胞への分化能の維持にとって必要である(PPARG is required for periodontal ligament cells to retain differentiation capacity of hard-tissue formation)

    Hang Yuan, Suzuki Shigeki, Sato Akiko, Yamamoto Tadahiro, Nemoto Eiji, Saito Masahiro, Yamada Satoru

    日本歯周病学会会誌　62　(春季特別)　125-125　2020/05

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

    eISSN： 1880-408X

  11. 炎症・メカニカル環境下における歯根膜細胞の新たな抗炎症システム 〜マクロファージIL-10 分泌誘導因子の発現〜 Peer-reviewed

    佐藤令, 丸山顕太郎, 向阪幸彦, 根本英二, 鈴木茂樹, 山田聡

    日本歯周病学会誌春季特別号　63　(春季特別)　144-144　2020/05

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

    eISSN： 1880-408X

  12. 精密マイクロパンチ加工で製作された純チタン多孔膜上における骨芽細胞様細胞培養 Peer-reviewed

    張井玉, 向阪幸彦, 丸山顕太郎, 石幡浩志, 鈴木茂樹, 根本英二, 山田 聡

    日本歯周病学会誌春季特別号　63　(141)　2020/05

  13. メカノレスポンス因子 MAP4K4 の歯根膜における発現とその機能解析 Peer-reviewed

    佐藤瞭子, 鈴木茂樹, 袁航, 山本真豊, 根本英二, 齋藤正寛, 山田聡

    日本歯周病学会誌春季特別号　63　(春季特別)　129-129　2020/05

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

    eISSN： 1880-408X

  14. 広汎型重度慢性歯周炎患者に対し非外科による特異的抗菌療法と歯周矯正,歯周補綴により包括的治療を行った一症例

    白石大祐, 白石大祐, 根本英二, 山田聡

    日本歯周病学会会誌(Web)　62　2020

    ISSN： 1880-408X

  15. メカノレスポンス因子MAP4K4の歯根膜における発現とその機能解析

    佐藤瞭子, 鈴木茂樹, HANG Yuan, 山本真豊, 根本英二, 齋藤正寛, 山田聡

    日本歯周病学会会誌(Web)　62　2020

    ISSN： 1880-408X

  16. 炎症・メカニカル環境下における歯根膜細胞の新たな抗炎症システム~マクロファージIL-10分泌誘導因子の発現~

    佐藤令, 丸山顕太郎, 向阪幸彦, 根本英二, 鈴木茂樹, 山田聡

    日本歯周病学会会誌(Web)　62　2020

    ISSN： 1880-408X

  17. Porphyromonas gingivalisジンジパインによりマスト細胞が産生するIL-31は、歯肉上皮細胞のclaudin-1発現を抑制しバリア破綻を誘導する

    多田浩之, 西岡貴志, 沼崎研人, 根本英二, 松下健二, 菅原俊二

    第73回日本細菌学会東北支部会　2019/08

  18. DMP-1遺伝子座アンチセンス非翻訳長鎖RNAによる口腔上皮由来細胞の遊走能制御

    鈴木 茂樹, 袁 航, 栗田 真夏, 大森 雅人, 根本 英二, 山田 聡

    日本歯周病学会会誌　61　(春季特別)　126-126　2019/05

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

    eISSN： 1880-408X

  19. 垂直性骨欠損に対してEMDおよび異種骨移植材を用いた歯周組織再生療法を行った一症例

    金谷 聡介, 根本 英二, 島内 英俊, 山田 聡

    日本歯周病学会会誌　61　(春季特別)　148-148　2019/05

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

    eISSN： 1880-408X

  20. 後天性てんかんを有する広汎型重度慢性歯周炎患者に対する早期インプラント埋入を含めた包括的歯周治療を行った一症例

    須藤 瑞樹, 根本 英二, 島内 英俊, 山田 聡

    日本歯周病学会会誌　61　(春季特別)　163-163　2019/05

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

    eISSN： 1880-408X

  21. 周期的伸展刺激を受容したヒト歯根膜細胞はマクロファージからのIL-10産生を促進する

    丸山 顕太郎, 根本 英二, 鈴木 茂樹, 山田 聡

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集　150回　98-98　2019/05

    Publisher: (NPO)日本歯科保存学会

  22. 積層した多孔性チタンメンブレン間の細胞遊走を利用した骨形成細胞の連続培養

    向阪 幸彦, 丸山 顕太郎, 張井 玉, 石幡 浩志, 根本 英二, 佐々木 啓一, 山田 聡, 初澤 毅

    生体医歯工学共同研究拠点成果報告書　平成30年度　87-87　2019/04

    Publisher: 東京医科歯科大学生体材料工学研究所

  23. 積層した多孔性チタンメンブレン間の細胞遊走を利用した骨形成細胞の連続培養

    向阪 幸彦, 丸山 顕太郎, 張井 玉, 石幡 浩志, 根本 英二, 佐々木 啓一, 山田 聡, 初澤 毅

    生体医歯工学共同研究拠点成果報告書　平成30年度　87-87　2019/04

    Publisher: 東京医科歯科大学生体材料工学研究所

  24. 垂直性骨欠損に対してEMDおよび異種骨移植材を用いた歯周組織再生療法を行った一症例

    金谷聡介, 金谷聡介, 根本英二, 島内英俊, 島内英俊, 山田聡

    日本歯周病学会会誌(Web)　61　2019

    ISSN： 1880-408X

  25. 後天性てんかんを有する広汎型重度慢性歯周炎患者に対する早期インプラント埋入を含めた包括的歯周治療を行った一症例

    須藤瑞樹, 根本英二, 島内英俊, 島内英俊, 山田聡

    日本歯周病学会会誌(Web)　61　2019

    ISSN： 1880-408X

  26. DMP-1遺伝子座アンチセンス非翻訳長鎖RNAによる口腔上皮由来細胞の遊走能制御

    鈴木茂樹, YUAN Hang, 栗田真夏, 大森雅人, 根本英二, 山田聡

    日本歯周病学会会誌(Web)　61　2019

    ISSN： 1880-408X

  27. 歯周病患者における機能指標としての咀嚼機能検査の有用性について

    宮沢 春菜, 中島 貴子, 松川 由実, 清水 伸太郎, 古市 保志, 根本 英二, 高井 英樹, 中山 洋平, 小方 頼昌, 岩崎 拓也, 石原 裕一, 大井 麻子, 齋藤 淳, 藤原 千春, 村上 伸也, 畑中 加珠, 高柴 正悟, 武田 克浩, 藤田 剛, 栗原 英見, 山崎 和久

    日本歯周病学会会誌　60　(秋季特別)　136-136　2018/10

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

    eISSN： 1880-408X

  28. ヒト歯根膜細胞は周期的伸展刺激により抗炎症性エクソソームを分泌する

    WANG Zhuyu, 根本英二, 丸山顕太郎, 鈴木茂樹, 多田浩之, 向阪幸彦, 須藤瑞樹, 山田聡

    日本歯周病学会会誌(Web)　60　118　2018/10/01

    ISSN： 1880-408X

  29. Porphyromonas gingivalisによるマスト細胞由来interleukin‐31を介した歯肉上皮細胞のclaudin‐1ダウンレギュレーション作用

    多田浩之, 西岡貴志, 根本英二, 松下健二

    日本歯科保存学会学術大会プログラムおよび講演抄録集(Web)　149th　141 (WEB ONLY)　2018/10

  30. 側枝検出可能な電気的根管長測定器での側技開放角度検出に関する研究

    庄司 茂, 丸山 顕太郎, 根本 英二, 山田 聡, 須藤 圭一

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集　149回　31-31　2018/10

    Publisher: (NPO)日本歯科保存学会

  31. ヒト歯根膜細胞は周期的伸展刺激により抗炎症性エクソソームを分泌する

    王 祝愉, 根本 英二, 丸山 顕太郎, 鈴木 茂樹, 多田 浩之, 向阪 幸彦, 須藤 瑞樹, 山田 聡

    日本歯周病学会会誌　60　(秋季特別)　118-118　2018/10

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

    eISSN： 1880-408X

  32. 他家脂肪組織由来多系統前駆細胞による前臨床研究について

    半田 慶介, 丸山 顕太郎, 根本 英二, 竹立 匡秀, 村上 伸也, 山田 聡, 齋藤 正寛

    日本歯周病学会会誌　60　(秋季特別)　120-120　2018/10

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

    eISSN： 1880-408X

  33. JDCP研究が示す我が国の糖尿病診療の現状 JDCP研究ベースライン時の歯周病所見

    稲垣 幸司, 菊池 毅, 野口 俊英, 三谷 章雄, 成瀬 桂子, 松原 達昭, 川浪 雅光, 根岸 淳, 古市 保志, 根本 英二, 吉江 弘正, 齋藤 淳, 富田 幸代, 片桐 さやか, 和泉 雄一, 新田 浩, 沼部 幸博, 山本 松男, 吉成 伸夫, 藤田 剛, 西村 英紀, 永田 俊彦, 内藤 徹, 野口 和行, 栗原 英見

    糖尿病　61　(Suppl.1)　S-89　2018/04

    Publisher: (一社)日本糖尿病学会

    ISSN： 0021-437X

    eISSN： 1881-588X

  34. チタン製メンブレンを用いた新規細胞培養法の開発

    向阪 幸彦, 丸山 顕太郎, 張井 玉, 石幡 浩志, 根本 英二, 佐々木 啓一, 山田 聡, 初澤 毅

    生体医歯工学共同研究拠点成果報告書　平成29年度　105-105　2018/04

    Publisher: 東京医科歯科大学生体材料工学研究所

  35. チタン製メンブレンを用いた新規細胞培養法の開発

    向阪 幸彦, 丸山 顕太郎, 張井 玉, 石幡 浩志, 根本 英二, 佐々木 啓一, 山田 聡, 初澤 毅

    生体医歯工学共同研究拠点成果報告書　平成29年度　105-105　2018/04

    Publisher: 東京医科歯科大学生体材料工学研究所

  36. 周期的伸展刺激を受容した歯根膜細胞はNLRP3インフラマソーム抑制因子を産生する

    WANG Zhuyu, 根本英二, 丸山顕太郎, 須藤瑞樹, 多田浩之, 山田聡

    日本歯周病学会会誌(Web)　59　(秋季特別)　196-196　2017/11/28

    Publisher: (NPO)日本歯周病学会

    ISSN： 1880-408X

  37. 周期的伸展刺激を受容した歯根膜細胞はNLRP3インフラマソーム抑制因子を産生する

    王 祝愉, 根本 英二, 丸山 顕太郎, 須藤 瑞樹, 多田 浩之, 山田 聡

    日本歯周病学会会誌　59　(秋季特別)　196-196　2017/11

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

    eISSN： 1880-408X

  38. 東日本大震災被災者における不眠症と口腔愁訴との関連

    土谷昌広, 相田潤, 萩原嘉廣, 菅原由美, 遠又靖丈, 佐藤眞理, 渡邉崇, 富田博秋, 根本英二, 渡邉誠, 小坂健, 小坂健, 辻一郎

    Pain Research　32　(2)　125-125　2017/06/16

    Publisher: (一社)日本疼痛学会

    ISSN： 0915-8588

  39. LIPUS刺激はNF‐κBシグナル抑制を介してIL‐1β分泌を抑制する

    須藤瑞樹, 丸山顕太郎, 金谷聡介, 金谷聡介, 根本英二

    日本歯科保存学会学術大会プログラムおよび講演抄録集(Web)　146th　25 (WEB ONLY)-25　2017/05/08

    Publisher: (NPO)日本歯科保存学会

  40. マクロファージ周期的伸展刺激はNLRP3インフラマソームを介したIL‐1βの分泌を抑制する

    丸山顕太郎, 須藤瑞樹, 向阪幸彦, 金谷聡介, 根本英二

    日本歯科保存学会学術大会プログラムおよび講演抄録集(Web)　146th　38 (WEB ONLY)-38　2017/05/08

    Publisher: (NPO)日本歯科保存学会

  41. 偏心モーター内蔵型振動スケーラーの歯石除去における有効性の評価

    丸山顕太郎, 池野修功, 小松秀裕, 向阪幸彦, 大方広志, 須藤瑞樹, 根本英二, 庄司茂

    日本歯周病学会会誌(Web)　58　131　2016/09/09

    ISSN： 1880-408X

  42. 高濃度細胞外カルシウム刺激に対する間葉系未分化細胞の反応性の解析~fibroblast growth factor2およびbone morphogenetic protein2の発現誘導~

    XIAO Binlu, 金谷聡介, 金谷聡介, 向阪幸彦, 須藤瑞樹, 齋藤正寛, 根本英二

    日本歯周病学会会誌(Web)　58　(秋季特別)　125-125　2016/09/09

    Publisher: (NPO)日本歯周病学会

    DOI： 10.2329/perio.58.125 　

    ISSN： 1880-408X

  43. 偏心モーター内臓型振動スケーラーの歯石除去における有効性の評価

    丸山 顕太郎, 池野 修功, 小松 秀裕, 向阪 幸彦, 大方 広志, 須藤 瑞樹, 根本 英二, 庄司 茂

    日本歯周病学会会誌　58　(秋季特別)　131-131　2016/09

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

  44. 未分化骨芽細胞細胞移植による歯槽骨再生療法について(第一報) ブタ歯槽骨由来未分化骨芽細胞の特性

    半田 慶介, 丸山 顕太郎, 根本 英二, 齋藤 正寛

    日本歯周病学会会誌　58　(秋季特別)　110-110　2016/09

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

  45. 未分化骨芽細胞移植を用いた歯周組織再生療法に関する研究

    半田 慶介, 二木 正晴, 丸山 顕太郎, 折本 愛, 石河 真幸, 根本 英二, 齋藤 正寛

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集　144回　53-53　2016/06

    Publisher: (NPO)日本歯科保存学会

  46. ヒト歯髄細胞への低出力超音波(LIPUS)はオステオポンチンの発現を誘導する

    須藤瑞樹, 金谷聡介, 金谷聡介, 島内英俊, 根本英二

    日本歯科保存学会学術大会プログラムおよび講演抄録集(Web)　143rd　P75 (WEB ONLY)-146　2015/11/01

    Publisher: (NPO)日本歯科保存学会

  47. ベルベリンはヒト歯根膜細胞アルカリフォスファターゼを抑制し細胞増殖を誘導する

    池野修功, 金谷聡介, 根本英二, 須藤瑞樹, 向阪幸彦, 島内英俊

    日本歯科保存学会学術大会プログラムおよび講演抄録集(Web)　143rd　B7 (WEB ONLY)　2015/11/01

  48. ナノハイドロキシアパタイトによる歯小嚢細胞のWnt/β‐cateninシグナル誘導

    向阪幸彦, 金谷聡介, 須藤瑞樹, 田村正人, 島内英俊, 根本英二

    日本歯周病学会会誌(Web)　57　126　2015/08/17

    ISSN： 1880-408X

  49. Non‐Canonical Wntがセメント芽細胞の分化に与える影響

    向阪幸彦, 根本英二, 須藤瑞樹, 金谷聡介, 田村正人, 島内英俊

    日本歯科保存学会学術大会プログラムおよび講演抄録集(Web)　140th　C5 (WEB ONLY)　2014/06/06

  50. Possible functional scaffolds for periodontal regeneration

    Hidetoshi Shimauchi, Eiji Nemoto, Hiroshi Ishihata, Masatsugu Shimomura

    Japanese Dental Science Review　49　(4)　118-130　2013/11

    DOI： 10.1016/j.jdsr.2013.05.001 　

    ISSN： 1882-7616

  51. 私の研究室から 完全な歯周組織再生を目指した高機能性スキャフォールドを求めて

    島内 英俊, 根本 英二, 石幡 浩志

    日本歯科評論　73　(10)　9-11　2013/10

    Publisher: ヒョーロン・パブリッシャーズ

    ISSN： 0289-0909

  52. ナノハイドロキシアパタイトによるBMP‐2発現誘導

    須藤瑞樹, 根本英二, 金谷聡介, 島内英俊

    日本歯周病学会学術大会プログラムおよび講演抄録集　55th　121　2012/04/10

    ISSN： 0385-0110

  53. Roles of IL-6 in Mastication in Mice and Effects of Training and Food Hardness Peer-reviewed

    Masahiro Tsuchiya, Tomomi Kiyama, Shinobu Tsuchiya, Hirohisa Takano, Eiji Nemoto, Keiichi Sasaki, Shunji Sugawara, Yasuo Endo, Makoto Watanabe

    Interface Oral Health Science 2011　104　2012

    Publisher: Springer Nature

    DOI： 10.1007/978-4-431-54070-0_21 　

  54. 第11回日本歯周病学会学術賞を受賞して(歯学情報、受賞報告)

    根本 英二

    東北大学歯学雑誌　30　(2)　53-53　2011/12/28

    Publisher: 東北大学歯学会

    ISSN： 0287-3915

  55. Non-canonical Wntシグナルによる骨芽細胞の分化抑制作用について

    江部 由佳梨, 根本 英二, 金谷 聡介, 土谷 昌広, 多田 浩之, 島内 英俊

    東北大学歯学雑誌　29　(2)　74-75　2010/12

    Publisher: 東北大学歯学会

    ISSN： 0287-3915

  56. Wnt signaling inhibits cementoblast differentiation Peer-reviewed

    Eiji Nemoto, Yohei Koshikawa, Sousuke Kanaya, Masahiro Tsuchiya, Masato Tamura, Martha J. Somerman, Hidetoshi Shimauchi

    Interface Oral Health Science 2009　113　2010

    Publisher: Springer Nature

    DOI： 10.1007/978-4-431-99644-6_16 　

  57. The effect of wnt signaling on murine cementoblast differentiation

    KOSHIKAWA Y, NEMOTO E, KANAYA S, SHIMAUCHI H

    50　41-41　2007/10/05

    ISSN： 0387-2343

  58. The expression of pattern-recognition receptors expressed by murine cementoblasts and its alteration during cell differentiation

    HONDA T, NEMOTO E, KANAYA S, SHIMAUCHI H

    50　46-46　2007/10/05

    ISSN： 0387-2343

  59. Analysis of Cell-Cell Adhesion between Dendritic Cells and Gingival Fibroblasts

    MINAMIBUCHI Maiko, KANAYA Sousuke, HONDA Toru, NEMOTO Eiji, SHIMAUCHI Hidetoshi

    48　127-127　2006/03/31

    ISSN： 0385-0110

  60. Retinoic acid is a potential negative regulator for differentiation of human periodontal ligament cells

    Natsuko Shibuya, Eiji Nemoto, Sousuke Kanaya, Ryotaro Kunii, Hidetoshi Shimauchi

    International Congress Series　1284　217-218　2005/09

    DOI： 10.1016/j.ics.2005.06.096 　

    ISSN： 0531-5131

  61. Expression of aminopeptidase N/CD13 on human gingival fibroblasts and upregulation upon stimulation with IL-4 and IL-13

    R. Kunii, E. Nemoto, S. Kanaya, T. Tsubahara, H. Shimauchi

    International Congress Series　1284　219-220　2005/09

    DOI： 10.1016/j.ics.2005.07.031 　

    ISSN： 0531-5131

  62. Expression of aminopeptidase N/CD13 on human gingival fibroblasts and up-regulation upon stimulation with Th2-type cytokines

    KUNII Ryotaro, NEMOTO Eiji, KANAYA Sousuke, TSUBAHARA Taisuke, SHIMAUCHI Hidetoshi

    46　102-102　2004/09/25

    ISSN： 0385-0110

  63. Elimination of ICAM-1 on human oral epithelial cells by gingipains from Porphyromonas gingivalis resulting in inhibition of neutrophil adhesion

    TADA Hiroyuki, NEMOTO Eiji, SHIMAUCHI Hidetoshi, TAKADA Haruhiko

    45　98-98　2003/09/25

    ISSN： 0385-0110

  64. Expression of CD73/ecto-5 '-nucleotidase on human gingival fibroblasts and contribution to the inhibition of interleukin-1 alpha-induced granulocyte-macrophage colony-stimulating factor production.

    R. Kunii, E. Nemoto, H. Tada, T. Tsubahara, H. Ishihata, H. Shimauchi

    JOURNAL OF DENTAL RESEARCH　82　B224-B224　2003/06

    ISSN： 0022-0345

  65. Porphyromonas gingivalis LPS induces the maturation of dendritic cells with CD14(+)CD16(+) phenotype.

    H. Shimauchi, S. Kanaya, E. Nemoto, T. Ogawa

    JOURNAL OF DENTAL RESEARCH　82　B218-B218　2003/06

    ISSN： 0022-0345

  66. Regulation of platelet-derived growth factor receptor-alpha and -beta on periodontal ligament cells during the formation of mineralited nodules in vitro.

    E. Nemoto, M. Shimonishi, Y. Nitta, H. Shimauchi

    JOURNAL OF DENTAL RESEARCH　82　B288-B288　2003/06

    ISSN： 0022-0345

  67. Proteolysis of ICAM-1 on human oral epithelial cells by cysteine proteinase, (Gingipains) from Porphyromonas gingivalis leading to down-regulation of neutrophil adhesion.

    H. Tada, S. Sugawara, E. Nemoto, N. Takahashi, T. Imamura, J. Potempa, J. Travis, H. Shimauchi, H. Takada

    JOURNAL OF DENTAL RESEARCH　82　B41-B41　2003/06

    ISSN： 0022-0345

  68. Expression of CD73/ecto-5'-nucleotidase on human gingival fibroblasts and contribution to the inhibition of granulocyte-macrophage colony stimulating factor production

    KUNII Ryotaro, NEMOTO Eiji, TADA Hiroyuki, TSUBAHARA Taisuke, ISHIHATA Hiroshi, SHIMAUCHI Hidetosi

    46　49-49　2003/05/06

    ISSN： 0387-2343

  69. Porphyromonas gingivalis LPS converts human dendritic cells (DC) into CD14^+CD16^+DC

    KANAYA S., NEMOTO E., OGAWA T., SHIMAUCHI H.

    45　85-85　2003/04/05

    ISSN： 0385-0110

  70. Leukocyte elastase cleaves CD40 expressed by gingival fibroblast leading to down-regulation of CD40-functions

    Nemoto E., Tsubahara T., Tada H., Kanaya S., Mayanagi G., Shimauchi H.

    Journal of the Japanese Association of Periodontology　44　97-97　2002/03/25

    Publisher: The Japanese Society of Periodontology

    ISSN： 0385-0110

  71. 慢性辺縁性歯周炎病巣からの歯周炎関連細菌26菌種のnested PCR法による検出

    真柳弦, 佐藤拓一, 根本英二, 島内英俊, 高橋信博

    歯科基礎医学会雑誌　44　(5)　2002

    ISSN： 0385-0137

  72. 好中球エラスターゼによる歯肉線維芽細胞のCD40の発現調節および機能調節機構の解析

    根本英二, 鍔原泰介, 多田浩之, 金谷聡介, 真柳弦, 島内英俊

    日本歯周病学会学術大会プログラムおよび講演抄録集　45th　2002

    ISSN： 0385-0110

  73. ヒト歯肉線維芽細胞におけるEndopeptidase24.11(CD10)およびAminopeptidase N(CD13)の発現とその調節機構の解析

    鍔原泰介, 根本英二, 真柳弦, 島内英俊

    日本歯周病学会学術大会プログラムおよび講演抄録集　45th　2002

    ISSN： 0385-0110

  74. 炎症反応における好中球エラスターゼの新たな機能 ― CD14依存性IL-8産生の選択的抑制機構― (日本炎症学会雑誌)

    根本英二, 島内英俊

    日本炎症学会雑誌　22　(1)　13-22　2002/01

    DOI： 10.2492/jsir.22.13 　

    ISSN： 1346-8022

  75. Elimination of CD14 on human gingival fibroblasts by gingipains from Porphyromonas gingivalis resulting in inhibition of lipopolysaccharide-induced interleukin-8 production

    Tada Hiroyuki, Nemoto Eiji, Takada Haruhiko, Shimauchi Hidetoshi

    Journal of the Japanese Association of Periodontology　43　117-117　2001/09/30

    Publisher: The Japanese Society of Periodontology

    ISSN： 0385-0110

  76. Potential negative feedback effect of human neutrophil elastase in an innate immunity mediated by human gingival fibroblasts

    Nemoto Eiji, Tada Hiroyuki, Takada Haruhiko, Shimauchi Hidetoshi

    Journal of the Japanese Association of Periodontology　42　128-128　2000/09/25

    Publisher: The Japanese Society of Periodontology

    ISSN： 0385-0110

  77. ヒト歯肉線維芽細胞膜上のCD26/dipeptidyl peptidase IV ―サイトカインおよび菌体成分による発現増強― (日本炎症学会雑誌)

    根本英二, 菅原俊二, 高田春比古, 庄司 茂, 堀内 博

    日本炎症学会雑誌　20　(5)　597-602　2000/05

    Publisher: The Japanese Society of Inflammation and Regeneration

    DOI： 10.2492/jsir1981.20.597 　

    ISSN： 0389-4290

    More details Close

    CD 26/dipeptidyl peptidase IV (DPPIV) is a cell surface ectoenzyme which participates in immune and inflammatory reactions. We found that CD 26 was only partially expressed on human fibroblasts from periodontal tissues, whereas fibroblasts from lung and skin expressed CD 26 constitutively as revealed by flow cytometry. We examined the possible upregulation of CD 26-expression on human gingival fibroblasts in response to various stimulants. Interleukin (IL) -1 α, tumor necrosis factor (TNF) -α, interferon (IFN) -γ, lipopolysaccharide (LPS) from Porphyromonas gingivalis, Prevotella intermedia, and Escherichia coli and Prevotella glycoprotein augmented CD 26 expression on gingival fibroblasts. Among the stimulants, IL-1 α exhibited the most potent activity. Enzymatic activity of CD 26 was also induced by stimulation on fibroblasts. The upregulation of CD 26 mRNA expression upon stimulation with IL-1 α was also revealed by a quantitative RT-PCR assay. In the kinetic experiment, 48 h and several days were required for maximum CD 26 mRNA accumulation and CD 26 molecule expression on the cell surface, respectively. The addition of cycloheximide almost completely inhibited the accumulation of CD 26 mRNA induced by IL-1 α. These results suggested that induction of CD 26 on human gingival fibroblasts is regulated at the transcriptional level, and is also dependent on a de nove synthesized protein factor (s) .

  78. Increase of CD 26/Dipeptidyl peptidase IV expression on Human gingival fibroblasts upon stimulation with cytokines and bacterial components

    NEMOTO Eiji, SHIMIZU Toshikatsu, SHOJI Shigeru, HORIUCHI Hiroshi

    42　63-63　1999/04/01

    ISSN： 0387-2343

  79. Histopathological Study of the pulpectomy and root canal enlargement by Er: YAG Laser

    SHOJI Shigeru, HARIU Hiromi, MITUTA Takayuki, NEMOTO Eiji, OKAGAMI Yoshihide, KATAOKA Kenzo, HORIUCHI Hiroshi

    42　73-73　1999/04/01

    ISSN： 0387-2343

  80. Root Canal Enlargenent by Er : YAG Laser using annular irradiation tip

    SHOJI Shigeru, HARIU Hiromi, NEMOTO Eiji, OKAGAMI Yoshihide, KATAOKA Kenzo, HORIUCHI Hiroshi

    40　47-47　1997/10/13

    ISSN： 0387-2343

  81. <講演抄録>6.リンパ球表面マーカーによる重度歯周炎患者スクリーニングの試み(第29回東北大学歯学会講演抄録)(一般演題)

    庄司 茂, 根本 英二, 石幡 浩志, 遠藤 英昭, 堀内 博

    東北大学歯学雑誌 = Tohoku University dental journal　15　(2)　192-192　1996/12/01

    ISSN： 0287-3915

  82. <講演抄録>5.早期発症型歯周炎患者における好中球の免疫学的解析(第29回東北大学歯学会講演抄録)(一般演題)

    根本 英二, 庄司 茂, 堀内 博

    東北大学歯学雑誌 = Tohoku University dental journal　15　(2)　191-191　1996/12/01

    ISSN： 0287-3915

  83. The evidence that promyelocytes are circulating in periphiral blood of patients with early onset periodontitis

    Nemoto Eiji, Shoji Shigeru, Horiuchi Hiroshi

    Journal of the Japanese Association of Periodontology　38　169-169　1996/09/05

    Publisher: The Japanese Society of Periodontology

    ISSN： 0385-0110

  84. Relationship between periodotal clinical symptoms and the lymphocyte surface marker in severe periodontal patients

    Shoji Shigeru, Endo Hideaki, Nemoto Eiji, Iiyama Masao, Sato Kimikazu, Kato Kiyosi, Isihata Hirosi, Yosida Kazusi, Saeki Kuniko, Hayakawa Jyunko, Iohara Misa, Sumitomo Michiko, Miura Chikako, Okada Ryouhei, Horiuchi Hiroshi

    Journal of the Japanese Association of Periodontology　38　161-161　1996/03/25

    Publisher: The Japanese Society of Periodontology

    ISSN： 0385-0110

  85. 抗溶連菌由来スーパー抗原により活性化されるT細胞の新しい生物学的意義． Invited

    岡本成史, 恩田時男, 菅原俊二, 根本英二, 力石秀実, 田村啓二, 熊谷勝男

    抗ウイルス化学療法の進歩（抗ウイルス化学療法研究会プロシーディング）　81-88　1994/07

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Books and Other Publications 11

  1. 歯内療法学専門用語集

    日本歯科保存学会, 日本歯内療法学会

    医歯薬出版　2023/03

    ISBN: 9784263455272

  2. 保存修復学専門用語集

    日本歯科保存学会

    医歯薬出版　2023/03

    ISBN: 9784263455289

  3. ザ・ペリオドントロジー = The periodontology

    沼部, 幸博, 梅田, 誠, 齋藤, 淳, 山本, 松男, 岩田, 隆紀, 小方, 頼昌

    永末書店　2023/02

    ISBN: 9784816014215

  4. 歯周病学

    根本英二、山田聡

    永末書店　2021/01

    ISBN: 9784816013829

  5. ザ・ペリオドントロジー 第３版

    根本 英二、山田聡

    永末書店　2019

  6. Extracellular phosphate increases bone morphogenetic protein-2 expression in human dental pulp cells and human periodontal ligament cells.

    NEMOTO Eiji

    Springer, Tokyo　2012

  7. Wnt signaling inhibits cementoblast differentiation.

    NEMOTO Eiji

    Springer, Tokyo,　2010

  8. Interface Oral Health Science 2009

    E. Nemoto, Y. Koshikawa, S. Kanaya, M. Tsuchiya, M. Tamura, MJ. Somerman, H. Shimauchi

    Springer, Tokyo　2009/04

  9. Interface Oral health Science 2007

    M. Minamibuchi, E. Nemoto, S. Kanaya, T. Ogawa, H. Shimauchi

    Springer, Tokyo　2008/03

  10. Interface Oral health Science

    S. Kanaya, E. Nemoto, T. Ogawa, M. Minamibuchi, T. Honda, H. Shimauchi

    Elsevier Ltd., London　2005/03

  11. Interface Oral Health Science

    R. Kunii, E. Nemoto, S. Kanaya, T. Tsubahara, H. Shimauchi

    Elsevier Ltd., London　2005/03

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Presentations 17

  1. Clinical Key Points of Periodontal Tissue Regeneration Therapy Invited

    Eiji Nemoto

    STOVIT ONLINE SERIES 2024 Universitas Airlangga Joint Symposium　2024/09/18

  2. 市民公開講座「歯周病の話題：口と全身の病気の危険な関係」 Invited

    根本英二

    第65回秋季日本歯周病学会学術大会　2022/09/03

  3. ホストケアから考える新しいプラークコントロールの実践 Invited

    根本英二

    日本臨床歯周病学会 40周年記念大会ランチョンセミナー　2022/07/30

  4. 歯根膜メカニカル環境とそのユニークな炎症制御の仕組み Invited

    根本 英二

    第 28 回内毒素・LPS 研究会、シンポジウム　2019/06/29

  5. 歯根膜メカニカル環境とエクソソームによるユニークな炎症制御の仕組み Invited

    根本 英二

    第75回東北大学歯学会 学術賞受賞講演　2019/06/14

  6. リグロス®による歯周組織再生療法 Invited

    根本 英二

    日本歯周病学会第5回東北地区臨床研修会 ランチョンセミナー　2019/03/17

  7. 学口のすすめ 〜お口から健康を考える〜 お口と全身の病気の危険な関係 Invited

    根本 英二

    平成３０年度みやぎ県民大学 大学開放講座　2018/12/08

  8. 「Exploratory Research on Cell Signaling-based Periodontal Regeneration」:Role of Wnt signaling on periodontal regeneration International-presentation Invited

    NEMOTO Eiji

    2015/10/30

  9. 「口と全身の病気の危険な関係」 Invited

    根本 英二

    仙台市教育局仙台明治青年大学講演会　2015/06/24

  10. 「歯の形態形成を調節する膜トランスポーターの生理機能」：歯髄細胞における細胞外カルシウムイオン／リン酸イオンによるBMP-2発現調節 Invited

    根本 英二

    第120回日本解剖学会全国学術集会、第92回日本生理学会大会合同大会 シンポジウム　2015/03/21

  11. 「歯周病と糖尿病の深い関係」 Invited

    根本 英二

    平成26年度仙台市青葉区保健所「歯と口腔の健康づくり」講演会　2014/11/21

  12. 歯周組織再生とレーザー」ハイブリッド体としての歯周組織とその再生メカニズム Invited

    根本 英二

    第13回日本歯科用レーザー学会学術大会 シンポジウム　2013/09/28

  13. 口腔再生医学の確立を目指した歯・歯周組織関連細胞の分化制御の分子機構 Invited

    根本 英二

    第55回日本歯周病学会春季学術大会学術賞受賞記念講演　2012/05/18

  14. 「歯周組織への感染とそれに対する免疫応答の特異性とは？」 歯周組織構成細胞による炎症反応制御システム―細胞膜表面酵素を中心に― Invited

    根本 英二

    第53回春季日本歯周病学会学術大会 シンポジウム　2010/05/14

  15. 歯周組織再生学におけるセメント芽細胞のバイオロジ？ Invited

    根本英二

    第４９回東北大学歯学会　2006/06/14

  16. Porphyromonas gingivalis LPS induces osteoclastogenesis in mouse cementoblasts through TLR-2 International-presentation

    E. Nemoto, R. Darveau, B. Foster, G. Noguera, M. Somerman

    35th American Association for Dental Research Annual Meeting　2006/03/08

  17. Porphyromonas gingivalis LPS induces osteoclastogenesis in mouse cementoblasts through TLR-2 International-presentation

    E. Nemoto, R. Darveau, B. Foster, G. Noguera, M. Somerman

    国際歯学会　2006/03/08

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Research Projects 51

  1. 歯周組織再生におけるRANK発現EVsの機能解析とその治療応用への基盤構築

    向阪 幸彦, 鈴木 茂樹, 根本 英二, 山田 聡

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 東北大学

    2024/04/01 - 2027/03/31

  2. 力学誘導M2マクロファージエクソソームによる新規歯周組織再生療法の基盤構築

    丸山 顕太郎, 向阪 幸彦, 根本 英二

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 東北大学

    2023/04 - 2026/03

  3. 高分化型セメント細胞エクソソームを軸としたセメント質形成と歯周組織再生への応用

    根本 英二, 鈴木 茂樹, 山田 聡

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 東北大学

    2023/04 - 2026/03

  4. 再生指向型エピゲノムに基づく歯周組織再生術前診断法と精密化療法の樹立

    鈴木 茂樹, 根本 英二, 山田 聡, 梶川 哲宏

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(B)

    Institution: 東北大学

    2024/04/01 - 2025/03/31

  5. 再生指向型エピゲノムに基づく歯周組織再生術前診断法と精密化療法の樹立

    鈴木 茂樹, 根本 英二, 山田 聡, 梶川 哲宏

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(B)

    Institution: 東北大学

    2022/04 - 2025/03

  6. RANKL逆シグナルと破骨細胞エクソソームを基軸とした新規歯周組織再生療法の開発

    向阪 幸彦, 鈴木 茂樹, 根本 英二, 山田 聡, 丸山 顕太郎

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 東北大学

    2021/04 - 2024/03

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    エクソソームは、細胞から分泌される膜小胞であり、タンパク質のみならずメッセンジャーRNAやマイクロRNAなども含めた膨大な情報伝達物質を他の細胞に伝達する役割がある。近年、破骨細胞が分泌するエクソソーム上に発現しているRANKが、骨芽細胞のRANKLと結合することで骨芽細胞の分化を誘導することが報告されている。一方でセメント質の研究に関しては、セメント芽細胞が発現しているRANKLが破骨細胞のRANKを介して破骨細胞分化を誘導することが報告されているが、破骨細胞由来のエクソソームがセメント芽細胞分化に与える影響については報告が皆無である。本研究の目的は、破骨細胞由来のRANK発現エクソソームによるセメント芽細胞の分化誘導を検証することである。 今年度は破骨細胞分泌エクソソームがセメント芽細胞に与える作用について検証した。まずマウスマクロファージ様細胞株RAW264.7をリコンビナントRANKL存在下にて5日間培養し破骨細胞分化を誘導した。その過程で培養3~5日目の上清を回収し、ExoQuick-TCエクソソーム単離キットを用いてエクソソームを単離した。セメント芽細胞の前駆細胞と考えられているマウス歯小嚢細胞株SVF4に単離したエクソソームで1日刺激した後にリコンビナントWnt3aで分化誘導を行ったところ、エクソソームの濃度依存的にSVF4のアルカリフォスファターゼ活性を抑制することを認めた。 次年度は上記の知見におけるシグナル解析を行うとともに、SVF4のRANKLの発現誘導あるいは抑制を行った条件下での破骨細胞由来エクソソームの作用を検討する。

  7. 疾患由来iPS細胞レジストリとPLAP-1を基軸とした侵襲性歯周炎の分子病態解明

    山田 聡, 森崎 隆幸, 江草 宏, 鈴木 茂樹, 根本 英二, 村上 伸也, 梶川 哲宏

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(B)

    Institution: 東北大学

    2020/04 - 2023/03

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    本研究では、未だその発症・進行メカニズムの詳細が不明な侵襲性歯周炎（AgP）において、患者由来iPS細胞レジストリ（AgP-iPS細胞レジストリ）を構築し、同細胞レジストリを用いて網羅的な全ゲノム解析と細胞分化機能解析を同時に行うことで、侵襲性歯周炎の原因となる複数の新たなる遺伝子変異群を決定することを目的としている。さらには、申請者らのこれまでの研究結果から、侵襲性歯周炎原因遺伝子の一つであることが示唆されるPLAP-1/Asporinについて、AgPレジストリにおけるPLAP-1遺伝子多型解析を行うことで、PLAP-1が、侵襲性歯周炎の原因遺伝子であることを証明することを目的としている。2021度は、侵襲性歯周炎患者由来iPS細胞レジストリ構築のため、侵襲性歯周炎患者の歯周基本治療および歯周外科処置時に通常は廃棄される不良肉芽組織を回収し、回収した組織からiPS細胞作製用の培養線維芽細胞を樹立するための学内倫理研究申請を行った。さらには、健常者由来iPS細胞を用いてiPS細胞の培養系ならびに間葉系間質細胞と骨芽細胞分化誘導系の確立を行っている。さらに、侵襲性歯周炎と診断された患者の末梢血からゲノムDNAを抽出し、同DNAを大阪大学侵襲性歯周炎ゲノムバンクへ送ることで、レジストリを構築した。また、PLAP-1遺伝子多型が見られるアスパラギン酸リピート数の差異がPLAP-1タンパクの機能におよぼす影響を解析することを目的として、リピート数の異なる哺乳類細胞由来組み換えPLAP-1タンパクを発現・作製するためのベクターシステムを構築した。

  8. WNT・メカノシグナルによる歯根膜幹細胞エクソソームの最適化と歯周組織再生制御

    根本 英二, 鈴木 茂樹, 山田 聡

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(C)

    Category: 基盤研究(C)

    Institution: 東北大学

    2020/04 - 2023/03

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    当該年度は，歯根膜組織に局在する細胞としてマウス由来セメント芽細胞に焦点を当てて研究を行なった。マウス由来セメント芽細胞由来エクソソームの破骨細胞分化誘導系に及ぼす影響について解析した。 マウスセメント芽細胞株OCCM-30の培養上清からエクソソームを抽出した。透過電子顕微鏡解析を行ったところ，直径約50～200 nmのエクソソームが存在することが確認された。マウス破骨細胞前駆細胞株RAW264.7細胞を，リコンビナントreceptor activator of nuclear factor-κB ligand（rRANKL）刺激により破骨細胞へ分化させる実験系を用いて，エクソソームの影響を調べた。エクソソームは，rRANKLによって誘導される酒石酸耐性酸性ホスファターゼ（TRAP）活性陽性細胞の形成を増強した。また，リアルタイムPCR法およびWestern blot法による解析から，エクソソームは，rRANKL刺激による破骨細胞関連遺伝子およびタンパクの発現誘導に対しても増強することが明らかとなった。一方，rRANKL非存在下では，細胞外小胞による破骨細胞分化増強作用は認められなかった。Western blot法の解析から，エクソソーム自体にはRANKLの発現は検出されなかった。一方，セメント芽細胞の細胞培養上清を用いて，rRANKL誘導性破骨細胞分化に与える影響について，TRAP活性陽性細胞の形成および破骨細胞関連遺伝子の発現の観点から調べた。細胞培養上清は，rRANKL誘導性破骨細胞分化を部分的に抑制するとともに，エクソソームによるその増強作用に対して，ほぼ完全に抑制することが明らかとなった。 以上のことから，セメント芽細胞から分泌されるエクソソームは，rRANKL誘導性破骨細胞分化に対して増強作用を有していることが明らかとなった。

  9. Retrospective quantitative analysis of juvenile stress using dentin matrix

    YAMADA SATORU

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Challenging Research (Exploratory)

    Institution: Tohoku University

    2020/07 - 2022/03

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    Mice were intravenously administrated corticosterone at early childhood or juvenile stage and the amount of corticosterone in mineralized hard tissue of their teeth was quantified by ELISA method. The results revealed that corticosterone was detected in mineralized hard tissue of the teeth of corticosterone-injected group but not PBS-injected control group. This result suggested that systemically administrated corticosterone could be deposited into hard tissue of teeth. Corticosterone level in circulation of the mice received early life stress was significantly higher than that of control mice (p=0.0019). Corticosterone level in hard tissue of the teeth of adult mice that have experienced early life stress was 0.5343 pg/mg and that of control adult mice was 0.3547 mg/kg (p = 0.2046). These results indicated that corticosterone induced by early life stress at early childhood stage possibly accumulated in hard tissue of the teeth and corticosterone level was retained during the lifespan.

  10. Roles of long non-coding RNAs for periodontal diseases

    Suzuki Shigeki

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2019/04 - 2022/03

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    By analyzing comprehensive RNA expression of gingival epithelial cells, promoter associated antisense long non-coding RNA (pan-lncRNA) was identified in DMP-1 gene locus. Loss of function assay by siRNA transfection and gain of function assay by over-expression showed that this pan-lncRNA was able to inhibit cellular migration ability by inhibiting EGF kinase activity. RNA immunoprecipitation assay with PP7 bacterial phage system reveled that this pan-lncRNA directly associated with nuclear-translocated EGFR to suppress STAT3 activity in EGFR-STAT3 complex.

  11. Constructing method for cementoblastic differentiation induced by 1alpha,25-dihydroxy Vitamin D3

    Kanaya Sousuke

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2017/04 - 2020/03

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    100nM 1alpha,25-dihydroxy Vitamin D3 enhanced Cementum protein 1 (CEMP1) and F-spondin gene expressions considered as specific cementoblastic markers in human periodontal ligament cells. 1alpha,25-dihydroxy Vitamin D3 also enhanced Osterix, Runx2, Alkaline phosphatase (ALP), Osteocalcin (OCN) and Bone sialoprotein (BSP) gene expressions which are regarded as important factors for osteoblastic and cementoblastic differentiation and mineralization. These results indicated that 1alpha,25-dihydroxy Vitamin D3 regulates periodontal ligament cells differentiation. Furthermore, Cells strongly expressed CEMP1 protein were appeared with long term 1alpha,25-dihydroxy Vitamin D3 stimulation. 100nM 1alpha,25-dihydroxy Vitamin D3 decreased mineralized nodule formation. 100nM 1alpha,25-dihydroxy Vitamin D3, Ascorbic acid, beta-glycerophosphate and dexamethazone enhanced mineralized nodule formation, however CEMP1 protein expression was decreased compared with 1alpha,25-dihydroxy Vitamin D3 alone.

  12. Ｗｎｔ・象牙質基質蛋白を軸としたセメント質形成制御理論の確立と歯周再生法への展開 Competitive

    根本 英二

    Offer Organization: 文部科学省

    System: 科学研究費補助金 基盤研究(B)

    2016/04 - 2020/03

  13. Bio-nonbio interface dental implant reinforcing prevention of oral biofilm by dual surface fabrication methods

    Shimauchi Hidetoshi, Taguchi Junji, Yoshikawa Ryouta, Fujimoto Yusuke

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2014/04 - 2018/03

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    The dental peri-implantitis is caused by adhesion of dental biofilm to the open surface of pure titanium. The purpose of this study is to establish a highly durable DLC film on the surface of the implant on the surface around the gingival margin, and innovative dental implant that is compatible with alveolar bone attachment and deterrence of biofilm adhesion such as dual-phase surface conditions of the biocompatible and anti-biofilm. As a result of depositing GCIB-DLC on the surface of pure titanium sample, it was confirmed that an adhesion strength of the DLC to the pure titanium surface is significantly high in comparison with a standard DLC coat. It could be applied to biofilm adhesion preventing type implants. In addition, GCIB-DLC showed an inhibitory effect on biofilm adhesion. We are going to examine biocompatibility and the safety by the animal test.

  14. Extracellular calcium increases gene expression of fibroblast growth factor-2 via a PKA and ERK1/2 pathway in mouse dental papilla cells.

    Kanaya Sousuke

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2014/04 - 2017/03

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    We have previously reported that elevated extracellular Ca2+ increased bone morphogenetic protein-2 (BMP-2) expression in human dental pulp (hDP) cells. In the present study, we examined the effect of extracellular Ca2+ on FGF-2 gene expression in immortalized mouse dental papilla cells (mDP). Extracellular Ca2+ increased FGF-2 gene expression in mDP. Gene expression of calcium-sensing receptor and G protein-coupled receptor family C group 6 member A, both of which are known to be sensors for extracellular Ca2+, was not detected in mDP. Ca2+-mediated Fgf-2 gene expression was reduced by pretreatment with H-89, a protein kinase A (PKA) inhibitor, or PD98059, an ERK1/2 inhibitor, but not by pretreatment with GF-109203X, a PKC inhibitor, or SB203580, a p38 inhibitor. These findings indicate that elevated extracellular Ca2+ increased Fgf-2 gene expression through PKA and ERK1/2 in mDP cells, and that this mechanism may assist in designing regenerative therapies for dentin.

  15. 平成２８年度知と医療機器創生拠点に係る補助金 Competitive

    根本 英二

    Offer Organization: 東北経済産業局

    System: J160000464地域イノベーション戦略支援プログラム

    2016/06 -

  16. 解離性大動脈瘤に対する新規イメージング診断技術開発に関する研究 Competitive

    根本 英二

    Offer Organization: 公益財団法人小林国際奨学財団

    System: 第５回研究助成金

    2016/04 -

  17. 低出力超音波パルスを基軸とした象牙質形成制御理論と非侵襲性歯内療法への展開 Competitive

    根本 英二

    Offer Organization: 文部科学省

    System: 科学研究費補助金 挑戦的萌芽研究

    2013/04 - 2016/03

  18. Development of a new strategy for regeneration of alveolar bone by combination of dental stem cells and the functional scaffold

    SHIMAUCHI Hidetoshi, ISHIHATA Hiroshi, NEMOTO Eiji, KANYA Sousuke

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: Tohoku University

    2013/04/01 - 2015/03/31

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    This research project was aimed to develop the new strategy of alveolar bone regeneration by a combination of dental stem cells and guided bone regeneration technique using a newly developed titanium (Ti) mesh membrane. Our in vitro studies revealed the molecular mechanisms of proliferation and differentiation of dental stem cells regulated by Wnt signaling. Dental folllicule cells (DFC) are able to differentiate into cement blast and alveolar bone cells. Canonical and non-canonical Wnt signaling performed the complementary role on DFC, that canonical Wnt3a signaling induced the osteoblastogenesis of DFC and non-canonical Wnt5a signaling negative developed these processes. Our newly developed Ti-mesh exhibited the proliferative effects on DFCs by a topographical effect. Furthermore, our animal studies indicated that a combination of graft and Ti-mesh induced the superior bone regeneration on standardized bone defect model made in beagle dogs.

  19. Creation of next generations of periodontal tissue engineering by applying honeycomb microarrays

    SHIMAUCHI Hidetoshi, ISHIHATA Hiroshi, NEMOTO Eiji, SUZUKI Osamu, KANAYA Sousuke, SHIMOMURA Masatsugu

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2011/04/01 - 2014/03/31

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    This research project was aimed to develop the new strategy for periodontal regeneration by combining both technologies of honeycomb microfilm (HF) and conditioning of the extracellular microenvironment for periodontal stem cells. As the result of studies, we indicated that: 1) a biodegradable polymer HF is suitable for the carrier of periodontal ligament cell sheet, 2) autocrine secretion of prostaglandin E2 is essential for the differentiation of periodontal cells stimulated with Ca2+ ion and mechanical stress, and 3) nano-hydroxyapatite could upregulated BMP-2 expression independent of ion release. Furthermore, OCP/ gelatin composite inlay increased angiogenesis as well as bone regeneration in the rat calvaria defect model. Our research results well established the foundations of new concept scaffold technology that can stimulate both cell proliferation and differentiation.

  20. Molecular mechanism of networking system between bone and hematopoietic cells via Wnt signaling pathway

    TAMURA Masato, NASHIMOTO Masayuki, NEMOTO Eiji, SATO Mari

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Hokkaido University

    2010/04/01 - 2014/03/31

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    Canonical Wnt signaling molecule such as Wnt3a down-regulated CXCL12 expression in murine ST-2 cells. The culture supernatant from Wnt3a-ST2 cells also reduced migratory activity of bone marrow-derived cells and hematopoietic cell in a migration assay. Screostin which inhibits canonical Wnt signaling is identified as a signaling molecule from osteocytes to hematopoietic cell. The expression of neuropeptide Y Y1 receptor mRNA was induced by BMP2. These results raise the possibility that NPY acts in osteoblasts and osteocytes via an autocrine mechanism. From this study, functional crosstalk of regulation between bone and the other tissue.

  21. Study of cementogenesis and Wnt signaling Competitive

    NEMOTO Eiji, SHIMAUCHI Hidetoshi, TAMURA Masato, TADA Hiroyuki

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2009/04 - 2012/03

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    Wnts are secreted glycoproteins that mediate developmental and post-developmental physiology through canonical and noncanonic al pathway. Although it appears that Wnt5a signaling supports normal bone physiology, the biological significa nce of noncanonical Wnts in osteogenesis is essentially unknown. In this study, we identified the expression of Wnt5a in osteoblasts in the tibial growth plate as well as bone marrow of rat tibia. Silencing gene expression of Wnt5a in cultured pre-osteobla st cells results in suppression of osteoblastic differen tiation, suggesting that Wnt5a signaling are of substantial importance for osteoblastic differentiation.

  22. Study of Dentin regeneration based on extracellular calcium and phosphate. Competitive

    NEMOTO Eiji, SHIMAUCHI Hidetoshi, KANAYA Sousuke, TADA Hiroyuki

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: Tohoku University

    2009/04 - 2012/03

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    It is one of the big aims of dentistry to reproduce a tooth substance (dentin)which is lost in caries. Growth factor BMP-2 regulates odontoblastic differentiation to make dentin. I clarified that the expression of BMP-2 gene was enhanced in human pulp cells upon stimulation with not only 10 mM calcium ion but also 3 mM inorganic phosphate via ERK/MAPK signaling pathway. This finding suggested possibility to be connected for a cure to enhance expression of BMP-2 in dentistry in future.

  23. Development of a sophisticated dental implant based on biomimetic engineering

    SHIMAUCHI Hidetoshi, ISHIHATA Hiroshi, NEMOTO Eiji, KANAYA Sousuke

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: Tohoku University

    2011 - 2012

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    This study was aimed to develop the new fabrication method that can fabricate an ideal surface structure on implant fixture to control the microscopic surface topography suitable for osseointegration and bone regeneration. For this purpose, we used “micro-dimple imprint method" by applying honeycomb films. We fabricated the regularly arrayed micro-dimple structure on the mirror-like finished surface of Type 1 Ti plate masked with honeycomb film by wet-etching. After the etching, we obtained the regularly arrayed dimples on Ti surface with identical diameter and pitch as a honeycomb mesh structure of the mask. Human periodontal ligament (hPDL) or STRO-1^+dental follicle (STRO-1^+DF) cells were seeded and culture on the honeycomb-fabricated and control Ti. hPDL/ STRO-1^+DF cells showed stimulated proliferation and a unique forms on the fabricated Ti, that is completely different from the uniformed pattern of cell behavior on control Ti surface, suggesting that our newly developed micro-dimple imprint method is useful for the processing of implant fixture surface and fabrication the surface topography at a μm order.

  24. Development of safe and clean low-temperature sterilization usingwater vapor plasma

    TAMAZAWA Kaoru, TAMAZAWA Yoshinori, NEMOTO Eiji

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2010 - 2012

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    The aim of this study was to generate stable H_2O plasma and to evaluate its efficacy of sterilization and biomaterial compatibility. As the results of that, 1) stable generation of H_2O plasma was possible by optimization the timing of air supply and an exhaust gas and application of ultra low-volume mass flow controller (0.02 g/min). 2) H_2O plasma showed high sterilization effect to kill 10^6 G. stearothermophilus spores wrapped with tyvec^R at 60oC in 10 min. 3) porus metal disc treated with H_2O plasma cleared standard cell compatibility.

  25. Creation of the new periodontal tissue engineering by dual delivery

    HIDETOSHI Shimauchi, EIJI Nemoto, KANAYA Sousuke, SUZUKI Osamu, SASANO Yasuyuki, KAMAKURA Shinji

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2008 - 2010

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    The purpose of this study is to develop the new concept of periodontal tissue regeneration which has a high-efficiency and is propagable to general dentistry. It was revealed that an application of newly-developed scaffold induced the proliferation and control of extracellular inorganic ion concentration induced the expression of a variety of cell growth factors, resulting in the enhanced proliferation and differentiation of periodontal component cells, as well as other hard tissue forming cells. Our study strongly suggested a possibility for the development of periodontal tissue engineering by applying controlled release of inorganic ions and surface topography of scaffold combined with cytokines, without using cell therapy.

  26. Analysis of Wnt signaling in cementoblast differention Competitive

    NEMOTO Eiji, SHIMAUCHI Hidetoshi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2007/04 - 2009/03

  27. Molecular mechanisms on differentiation or function of osteoblasts and osteoclasts by the Wnt/LRP signaling pathway

    TAMURA Masato, NASHIMOTO Masayuki, NEMOTO Eiji, ISHISAKI Akira

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Hokkaido University

    2007 - 2009

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    In this study, we demonstrated that two cellular signaling pathways of Wnt and bone morphogenetic protein (BMP) control both differentiation and function of osteoblasts and osteoclasts during processes of bone formation and resorption. These Wnt and BMP signaling regulates osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor, which can inhibit the production of osteoclasts. The regulation of OPG expression is mediated through two transcription pathways such as Wnt and BMP that involve the OPG promoter. We also demonstrated that osteoblastic differentiation mediated by certain miRNA expression and BMP-2 down-regulates miR-206 expression at the post-transcriptional level and that BMP-2 could regulate miRNA biogenesis by a novel mechanism.

  28. Development of safe and clean sterilization method using low temperature plasma

    TAMAZAWA Kahoru, TAMAZAWA Yoshinori, NEMOTO Eiji, KANAYA Sousuke

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2006 - 2008

  29. 細胞外Ca2+によるセメント芽細胞制御機構の解明と新規歯周医療の探索 Competitive

    根本 英二

    Offer Organization: 東北大学平成１９年度特別教育研究経費

    System: 生体—バイオマテリアル高機能インターフェイス科学推進事業に関連するインターフェイス研究推進プログラム

    2007/04 -

  30. サイトカイン徐放性を有する歯周組織再生deviceの開発

    島内 英俊, 鈴木 治, 笹野 泰之, 鎌倉 慎司, 根本 英二

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 萌芽研究

    Institution: 東北大学

    2005 - 2006

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    本研究の目的は、歯周組織を構成する細胞の増殖・分化のステージに応じた複数のサイトカインの選択的投与が必要という考えから、担体そのものにサイトカインを結合させて徐放させるというシステムを開発することである。平成17年度においては、OCP加水分解物(fiuoridated Ca-deficient HA ; F-HA)をラット頭蓋冠欠損モデルに埋入したところ有意に高い骨再生が得られ、F-HAが代替骨として非常に有用であることをまず示した。本年度はまず骨芽細胞系のST-2のOCPあるいはHAコートディッシュ上での増殖と分化を調べたところ、ST-2のOCP上での細胞増殖は初期において阻害されるものの石灰化能は培養終期に急速に増加することが明らかにあり、OCPは骨芽細胞によってHAに転換されることで硬組織形成を促進することが示された。一方、硬組織形成を促進するサイトカインであるBMP-2とOCPを同時にラット頭蓋冠欠損モデルに移植したところ、顕著に骨再生を促進することが明らかとなった。この作用をin vitroで解析したところ、BMP-2活性は吸着温度条件に依存することが示された。さらにBMP-2吸着はOCPの表面結晶構造により異なることも明らかとなった。マラッセ上皮細胞からの産生が報告されているIGF-IおよびIGF-IIを用いて、マウスセメント芽細胞に分化に与える影響を検討した。その結果、IGF-IIの刺激によって、osteogenic geneのオステオカルシン、骨シアロプロテイン遺伝子発現が有意に亢進することが明らかとなった。また、分化マーカ・一であるアルカリンフォスファターゼの発現も弱いながらも誘導されることが分かった。IGF-Iの刺激においては、著明な変化は見られなかった。一方、セメント芽細胞の前駆細胞と考えられているマウス歯小嚢細胞ではこれらの遺伝子発現はむしろ抑制されることが明らかとなった。すなわち、IGF-IIの作用はtargetとなる細胞の分化段階に大きく依存していることが示唆された。

  31. Analysis of Molecular and Biological Basis of Systemic Effects Provoked by Periodontal Diseases

    SHIMAUCHI Hidetoshi, KANAYA Sousuke, ITAGAKI Yumi, SUGAWARA Shunji, TAKAHASHI Nobuhiro, SHOJI Kanako

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku university

    2004 - 2006

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    The purpose of this study is to explore the unidentified "missing link" to connect the relationship between periodontal and systemic diseases by molecular biological approaches. For this purpose, we focused on the most potent pathogen of chronic periodontitis, Porphyromonas gingivalis and its components, and analyzed the molecular basis of exerting virulence of this bacterium on both periodontal lesions and bodies in vivo and in vitro. Using in vivo animal models, we investigated a series of studies clarifying ; 1)the role of P.gingivalis infection on hyperlipidemia in periodontitis patients ; 2)the effect of P.gingivalis virulence factors on production of adipocytokines from adipose tissues ; 3)the molecular effects of type 2 diabetes on the healing process of periodontium. First, our in vitro study revealed that P.gingivalis LPS and fimbriae preferentially induced a unique dendritic cell subset with a weak immunostimulatory activity via TLR2-mediated signaling, finally contributing to the immune escape of this bacterium in the periodontal lesion. Furthermore, in vivo studies indicated that infection of P.gingivalis is essential for up-regulation of serum triglycerides and its LPS down-regulated the serum level of adiponectin, suggesting P.gingivalis could exert its virulence after invasion into the systemic circulation. The concept of metabolic syndrome (MetS) has been evolving, that is a clustering of simple clinical measures including waist circumferences, blood pressure, triglycerides, high-density lipoproteins and glucose. This clustering appears depend on two major factors: excess body fat and metabolic susceptibility. Taken our results into this concept, invaded P.gingivalis may work as a MetS risk factor in periodontitis patients via down-regulating the serum adiponectin level. The increased risk of MetS possibly started the sequential of "Metaboic Domino" that increasing the susceptibility to diabetes and coronary heart diseases. Diabetes can delay the healing process of periodontally diseased tissue that may increase the chance of P.gigivalis invasion. In conclusion, P.gingivalis may have an adaptation system by dealing with the local immune defense that finally contributes to systemic-periodontal connection.

  32. The research of effect to mind operation caused by dental cutting noise and vibration through bone conduction.

    SHOJI Shigeru, YAMAKI Keiko, ISHIHATA Hiroshi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2004 - 2005

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    People haven't liked the dental treatment and tried to avoid going to a dental clinic. The main reason of this avoidance was the peripheral nervous pain during dental treatment. Then the dental treatment machine, for example air-turbine and electric handpiece, caused the cutting noise and vibration which were conducted to brain tissue through the cranium. We thought these stimulation caused depression and mental pain of the patients. To clear of the mental change, we observed the brain waves of mind operation. On the otherhand, we have many old patients who had heart disease and lung disease. So in this study, we measured the heart beats by SpO2 and air-pad sensor, respiratory rate by air-pad sensor and blood pressure by fina-press. And to observe the change of stress and pain, we measured the change of respiration by GSR. To analyze the recorded data, we used LabVIEW. Under the Helsinki declaration, we had twelve volunteers who understood the object of this study. As the experimental stimulator, we used an ultrasonic scaler (full, 70% and 50% power). To certificate of the change of patient, we recorded the video picture by USB camera. The results of this study, 1,The pain and stress caused by the scaling lead the change of peak interval length, like R-R length. 2,Air-pad sensor was able to record the body conditions as like as the previous established recorders. These results supported the possibility which the air-pad sensor could find the change of patient's mind operation and body condition. So we thought this air-pad sensor could detect the sign of body condition and protect the aggravation during the dental treatment.

  33. 歯根膜細胞による硬組織形成機構の解析およびそれに基づいた歯周組織再生療法の開発 Competitive

    根本 英二

    Offer Organization: 上原記念生命科学財団

    System: 研究奨励

    2004/04 -

  34. 好中球プロテアーゼによる歯肉上皮系創傷治癒の制御機構の解析 Competitive

    根本 英二

    Offer Organization: 文部科学省

    System: 科学研究費補助金 若手(B)

    Category: 若手研究(B)

    Institution: 東北大学

    2002/04 - 2004/03

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    本研究はエラスターゼの炎症反応調節因子としての作用を検討した。まず、歯肉線維芽細胞に対するエラスターゼの影響を検討した。同細胞上に発現する炎症反応調節機構に重要なCD40に着目したところ、エラスターゼは細胞膜上でのProteolysisを介してその発現を消失させ、CD40からめ刺激によるケモカィン(IL-8およびMCP-1)の産生を抑えることを証明した(J.Leukoc.Biol.2002)。線維芽細胞による抗炎症作用に働くCD73 (J.Periodontal Res.2004)に対してはエラスターゼの分解作用は見られなかった。また、細菌由来のセリン系プロテアーゼ・ジンジパインを用いて同様の実験を行ったところ、CD14に対する同様の作用機序にてLPSに対するIL-8産生を低下させることが分かった(Infect.Immun.2002)。すなわち、生体の産生するプロテアーゼは過剰な炎症反応に対するフィードバック機構として、細菌由来のプロテアーゼは生体防御反応機構を低下に関与していることが示唆された。次に、歯肉上皮細胞に対するエラスターゼおよびジンジパインの影響を検討した。ジンジパインにおいては、上皮細胞上のICAM-1を選択的に分解し、ICAM-1を介した好中球との結合能が阻害されることがわかった。すなわち、上皮細胞においても生体防御反応機構を低下に関与していることが示唆された(J.Dent.Res.2003)。エラスターゼの上皮細胞に与える影響においては、上皮系創傷治癒に重要な各成長因子受容体に焦点を当てて検討した。上皮成長因子受容体(EGFR)に発現が僅かに高まることが蛋白レベルで分かった。この発現亢進機構には細胞内シグナル伝達過程でホスフォリパーゼCが関与していることがインヒビターを用いた実験から明らかとなった。

  35. Novel bioactivities of neutrophil serine proteases against periodontopathic bacteria in innate immunity

    SUGAWARA Shunji, TAKADA Haruhiko, NEMOTO Eiji, ENDO Yasuo

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2003 - 2004

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    Research results of this project are as follows, 1.Neutrophil serine proteases (elastase, cathepsin G, and proteinase 3 (PR3)) activate human non-epithelial cells (i.e.human gingival fibroblasts (HGF)) through G-protein-coupled protease-activated receptor-2 (PAR-2) and induce cytokine production from the cells. PR3 but not elastase and cathepsin G activates oral epithelial cells, due to secretory leukocyte inhibitor (an inhibitor of elastase and cathepsin G but not PR3) from the epithelial cells. 2.Inflamed oral epithelium expresses PR3. Proinflammatory cytokines induce PR3 as membrane-bound and secretory forms with enzymatic activity. Antibodies to PR3 activate the cells through PAR-2 and induce chemokine production from the cells. 3.As T cells accumulate in the inflamed lamina propria of gingival tissue from patients with adult periodontitis, immune responses of gingival cells to T cell cytokines, interleukin-2 (IL-2) and IL-15 was investigated. Endogenous IL-15 expressed in HGF sustains recruitment of IL-2/15 receptor β and common γ through nuclear factor-κB activation in normal and inflamed HGF. 4.A trypsin-like proteases, gingipains, from periodontopathic bacteria cleave intercellular adhesion molecule-1 (CD54) expressed on oral epithelial cells, and consequently disrupt neutrophil-oral epithelial cell interaction. 5.SalivaCD14, an important molecule in innate immunity, promotes the invasion of oral epithelial cells by periodontopathic bacteria and consequently augments the production of chemokine, playing an important role in innate immunity in the oral cavity.

  36. 歯周組織構成細胞の相互作用に基づく新たな歯周組織再生誘導機構の解析 Competitive

    根本 英二

    Offer Organization: 武田科学振興財団

    System: 一般研究奨励

    2003/04 -

  37. Periodontal Diseases as a Hypersensitivity Reaction Based on Innate Immune Responses in Periodontal Tissues

    TAKADA Haruhiko, UEHARA Akiko, FUNAYAMA Hitomi, SUGAWARA Shunji, TADA Hiroyuki

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2002 - 2003

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    We performed studies based on the hypothesis that "in periodontal tissues in which numerous bacteria inhabit and interact with the cells, host defense systems, especially innate immune systems, are activated constitutively, resulting in hypersensitivity-like reactions leading to tissue destruction and periodontal diseases". The major findings were as follows. 1)Innate immune responses of oral epithelial cells : Human oral epithelial cells could not respond to endotoxic lipopolysaccharide [LPS; Toll-like receptor (TLR) 4 ligand], peptidoglycans (PGN; TLR2 ligand), and muramyldipeptide (MDP; intracellular receptor, NOD2 was discovered in the last year), while they responded to some cell-surface components of periodontopathic bacteria. Interferon-γ(IFNγ)-treated human oral epithelial cells responded to various bacterial components to produce inflammatoty cytokines. 2)Innate immune responses of fibroblasts in periodontal tissues : Human gingival fibroblasts carrying membrane CD14 (mCD14) responded to LPS, while human periodontal ligament fibroblasts carrying much TLR2 but lacking mCD14 could not respond. to LPS, but responded to PGN. IFNγ-treated human gingival. fibroblasts exhibited marked response to-various bacterial components, accompanied by up-regulation of mCD14 and Myd88, which is a common adaptor molecule for TLRs. Gingipains produced by Porphyroinonas gingivalis cleaved mCD14 on human gingival fibroblasts, resulting in hypo-responsiveness to. LPS. 3)Soluble CD14 (sCD 14) in human saliva : Human salivary gland cells, especially parotid gland cells, produced sCD14: The sCD14 concentration in parotid saliva was comparable to that in human serum. Salivary sCD14-augmented the incorporation of Actinobacillus actinomycetemcomitans by oral epithel oral cells, resulting in the enhancement of the innate immune responses of the cells. 4)TLR4 agonistic activity of fungal mannan : Fungal cell-wall mannan, including that from oral Candida albicans, activated human monocytic cells in a CD14-and TLR4-dependent manner.

  38. RELTION BETWEEN PERIODONTAL STATUS AND CARDIOVASCULAR RISK FACTORS

    TAMAZAWA Kaoru, ITAGAKI Yumi, TAMAZAWA Yoshinori, SHIMAUCHI Hidetoshi, NEMOTO Eiji

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2001 - 2003

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    Hypertension (HT), hyperlipidemia (HP) and smoking habit (SH) are major risk factors for cardiovascular disease (CVD). The purpose of this study is to investigate the association between periodontal status (PHS) and major risk factors for CVD. The subjects are patients who undergo treatment for a HT in an affiliated hospital of our university. The following parameters were examined. Examination of CVD : age, gender, family history, medical history, history of smoking, lifestyle, blood pressure (SBP,DBP,MBP,PP), pulse wave velocity (PWV), blood examination (TCH,HDL,LDL,TG,BUN,UA,Cr,FBS,HbA1c), obesity index, medications. Examination of PHS : probing depth (PD), bleeding on probing (BOP), GI, plaque index, coated tongue score, breath odor. Examination of bacteria : saliva, sub-gingival plaque. <Results>The subjects were divided into 2 groups : the risk group with a HT and the high-risk group with a HT and a HP or with a HT and a SH. There were significant differences in BOP (p<0.05) and GI (p<0.01) between high risk group with a HT and a SH (n=32) and the risk group (n=39). This suggested that there may be associated with PHS arid CVD. Porphyromoncis gingivalis (Pg), is putative periodontal pathogens, cannot becultivated in all of 142 samples. On the other hand, Pg prevalence detected by real time PCR was 90 % (9samples out of 10). PCR methods have been used for detection of microorganisms that cannot be cultivated but these methods have given cross-reactions with related organisms. In the future, we should collect more data to clarify correlation to PHS and CVD used by the method to accurately detect species in mixed bacteria populations

  39. The analysis of tissue regeneration of pulp tissue using the derivation on stem cell differentiation

    SHOJI Shigeru, NEMOTO Eiji, YAMAKI Keiko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2001 - 2003

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    The fragility of pulp-less tooth has been well known. Besides the loss of time and money through the root canal treatment for a patient and a dentist. To solve this problem, we thought that it was worthwhile for pulp treatment to derive the partial pulp tissue using the derivation on stem cell differentiation. Recently the development of research on cell facial antigen of embryonic stem cell (ES cell) has been remarkable. Especially the Stage Specific Embryonic Antigen-1 (SSEA-1) stained the cell facial antigen of ES cell, Embryonal Carcinoma cell (EC cell) and Embryonic Germ cell (EG cell) on mouse, and on human cell SSEA-1 stains just only EG cell. But the Stage Specific Embryonic Antigen-4 (SSEA-4) stains all human ECIES and EG cell, and this SSEA-4 could not be observed in mouse cells. We stained these antigens on human and mouse pulp tissue cells. On human cells we could observe all ES,EC and ES antigens. Then this 2003 we tried to stain another antigen (Tumor Rejection Antigen-1-60: TRA-1-60) and TRA-1-81. we could stain these antigen on human pulp cells. But we could not bather the human pulp tissue under the definite condition. We must advance the immunohistochemical research under the definite condition using mouse cells. Moreover we need the establishment to distinguish the difference among the ES,EC and EG cells. If we can establish these difference, we will get the pulp tissue regeneration using the derivation on stem cell differentiation.

  40. Development of a new diagnostic strategy of periodontal disease based on the gene profile associated with host defense mechanisms.

    SHIMAUCHI Hidetoshi, IKAWA Motohide, IIYAMA Masao, NEMOTO Eiji, OGAWA Tomohiko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: TOHOKU UNIVERSITY

    2001 - 2003

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    The purpose of this study is to develop a new diagnostic strategy based on the gene profile that determine the host-parasite interaction occurring in periodontal disease lesion. We have successfully developed 2 methods applying the sensitive PCR technique ; 1)RT-PCR of 16sRNA genes to detect 25 periodontopathic bacteria from small amount of plaque samples, 2)real-time PCR protocol for quantification of multiple cytokine mRNA levels in the gingival tissue biopsies from periodontal disease patients. For microbial analyis, Genomic DNA was extracted from subgingival and supragingival plaque samples, and bacterial detection was performed by PCR of the 16S rRNA genes. the detection frequencies of 11 bacteria including Porphyromonas gingivalis, Treponema denticola and Prevotella intermedia in subgingival plaque were significantly higher in Periodontitis (P) group than in Healthy (H) group. P. gingivalis was detected only in P group, suggesting this bacterium as the candidate for identifying periodontal diseases. The bacteria flora of supragingival plaque was also found to reflect that of subginginval plaque. Real-time PCR detection of cytokine mRNA showed a comparable levels of semi-quantitative conventional RT-PCR. We next applied the real-time technique for the quantification of multiple cytokine gene levels, and compared the mRNA levels with clinical parameters. Among the target cytokines in this study, IL-6 and IL-1α showed a positive and strong association with PPD and GI. IL-1ra mRNA levels of gingival specimens from periodontitis patients were consistently high, suggesting the evoke of immunosuppressive activity in periodontal lesion. Our data suggest that these protocols could provide powerful insights into the complexities of the cytokine network and host-parasite interactiuon. The elucidation of the network may clarify the mechanisms of disease sensitivity at individual level and disease activity at site level.

  41. 歯肉線維芽細胞の自然免疫反応に対する好中球による調節機構の解析 Competitive

    根本 英二

    Offer Organization: 文部科学省

    System: 科学研究費補助金 奨励(A)

    2000/04 - 2002/03

  42. Regulation of oral mucosal immunity in human oral epithelial cells and periodontitis

    SUGAWARA Shunji, NEMOTO Eiji, TAKADA Haruhiko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2001 - 2002

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    1. Oral epithelial cells constitutively express precursor form of interleukin-18 (IL-18) in the cells. Bioactive IL-18 was produced from the cells on costimulation with neutrophil serine proteinase, proteinase 3 (PR3), and Iipopolysaccharide (LPS) after interferon-γ (IFN-γ)-priming. PR3 was found to activate oral epithelial cells through G protein-coupled protease-activated receptor-2. 2. Oral epithelial cells do not express a bacterial pattern recognition receptor, CD 14, and express Toll-like receptors (TLRs)/MD-2/MyD88 system, which is critical in innate immune recognition. However, the cells are refractory to bacterial components even in the presence of soluble CD14, The cells are able to respond to components from black-pigmented bacteria (BPB). The cells acquire responsiveness to many bacterial components after priming with IFN-γ. 3. Nonendotoxic glycoprotein from BPB activates host cells in a CD14- and TLR2-dependent manner. 4. CD14-expreswsing human gingival fibroblasts (HGF) have the same property with oral epithelial cells. Human periodontal ligament fibroblasts (HPLF) express TLR2 more strongly than HGF. HGF mainly respond to Gram-negative, and HPLF mainly respond to Gram-positive bacterial components, respectively. Cysteine proteinases (gingipains) from periodontopafhic bacteria degrade CD14 on HGF, consequently, suppress CD14-dependent responsiveness to bacterial components. 5. Human salivary glands constitutively express CD14 and secrete as a soluble form in saliva.

  43. Analysis of Mechanism for Specific Immune Response Induction to Periodontopathic Bacteria

    SHIMAUCHI Hidetoshi, IIYAMA Masao, NEMOTO Eiji, ENDOH Hideaki

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: TOHOKU UNIVERSITY

    2000 - 2002

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    Primary immune responses are initiated by dendritic cells (DC), which inform naive Th cells about invading pathogens. DC settle as interstitial DC and Langerhans cells in peripheral non-lymphoid tissues including gingiva. These peripheral DC capture and process Ag at the site of inflammation, and then migrate to lymph nodes to prime Th cells. DC undergo a series of events leading to irreversible maturation upon stimulation with invading bacteria, and up-regulate cytokine production and surface molecule expression with different kinetics. To investigate the responses DC during periodontal infection, we analyzed (1)the sensitivitly to Human Leukocyte Elastase (HLE) digestion of CD40 on DC, (2)the effects of LPS and fimbriae from P. gingivalis on the phenotype of human in DC. CD40 on DC was resistant to HLE treatment, unlike the molecule of human gingival fibroblasts, suggesting that DC were capale to stimulate the local immune responses after PMNL infiltration. Furthermore, P. gingivalis LPS and fimbriae preferentially up-regulated CD14 and CD16 expression on immature PBDC (CD14^-CD16^-), although E. coli LPS did not alter the expression of these molecules. P. gingivalis LPS-induced CD14^+CD16^+ cells strongly expressed dendritic cell markers: Cdla and HLA-DR, and CD54 was highly expressed. However, CD40, CD80, CD83, CD86 expression was lower than E.coli LPS-stimulated DC, suggesting these cells were in DC with weak immunnostimulatory activity. P.gingivalis LPS was a weaker stimulator in terms of IL-6, IL-8, IL-10, IL-12, and RANTES production from DC as compared to E.coli LPS. Both LPS stimulated-DC induced comparable up-take of dextran-FITC, although P.gingivalis induced the statistically weaker allogenic T cell proliferation. These results suggestively indicated P. gingivalis LPS and fimbriae trigger a maturation of DC with unique characteristics, that modulate immune responses occurred at the site of periodontal infection. P.gingivalis-induced CD14^+CD16^+DC subsets may contribute to induction of chronic inflammation.

  44. 歯髄疾患ならびに歯牙移植への応用を目指した細胞賦活化法の開発

    島内 英俊, 八巻 恵子, 石幡 浩志, 根本 英二

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 萌芽的研究

    Institution: 東北大学

    2001 - 2001

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    従来から低出力レーザー照射により骨芽細胞あるいは歯根膜細胞の増殖や石灰化が促進することが知られている。本研究はこのような低出力レーザーのヒト細胞への作用効率を最大限に高めて歯髄細胞や歯周組織構成細胞を賦活化して、保存あるいは再生療法に応用しようというものである。まず出力3mWの赤外光(830nm)ならびに可視光(670nm)レーザーをヒト口腔上皮由来KB細胞に照射し炎症性サイトカイン産生に及ぼす影響を検討した。その結果、いずれの波長のレーザーも1.8Jの照射でKB細胞からのspontaneousなIL-8産生を有意に抑制することが明らかとなった。これは低出力レーザー照射が歯肉上皮細胞からのケモカイン産生の抑制を介して抗炎症的に働くことを示唆するものと考えられた。しかし、3mWの出力では旋光抽出条件や照射時間を変えても、歯肉線維芽細胞(HFG)や歯根膜細胞(PDL)機能に影響を与えることはできなかった。そこで我々の予備研究から、可視〜赤色光領域に比べて生体組織による吸収・散乱が大きい短波長領域のレーザーを用いることとした。すなわち、波長532nm、出力150mWのレーザーを用いて、12.6Jの照射をHGFに行ったところ、陽性対照としたIL-1刺激の場合に比べて5分の照射時間で有意に高いGM-CSF産生を生じることが明らかとなった。さらに、この照射条件では未照射群に比べて細胞のviabilityに低下は認められなかった。今回の結果より、歯肉上皮細胞に対しては低出力レーザーがケモカインの産生抑制を介して抗炎症的に働くこと、HGFなどの深部歯周組織を構成する細胞については、従来の報告よりも低出力の短波長域レーザーの照射により効率的に細胞機能を制御できることが明らかとなった。

  45. Recognition of Cell-Surface Components of Bacteria in Innate Immune System, with Special Reference to the Role of Toll-Like Receptors

    TAKADA Haruhiko, NEMOTO Eiji, SUGAWARA Shunji

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2000 - 2001

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    Toll-like receptors (TLR) are involved in the ability of the host innate immune system to recognize microbial patterns. We studied recognition of various bacterial components by the host innate immune system, especially cells in periodontal tissues, in relation to the pathogenesis of mucosal diseases in the oral cavity. We obtained the following findings, (l) Three cysteine proteases, gingipains, from periodontopathic Porphyromonas gingivalis cleaved membrane C 14 (mCD14) on human monocytes, leading to lipopolysaccharide (LPS) hyporesponsiveness of the cells. (2) Human leukocyte elastase cleaved mCD14 on human gingival fibroblasts (HGF), resulting in LPS hyporesponsiveness of the cells. (3) Gingival epithelial cells that lacked mCD14 did not respond to LPS, peptidoglycan (PGN), muramyldipeptide (MDP) which is a critical moiety of PGN, or lipoteichoic acids (LTA) from gram-positive bacteria even in the presence of soluble CD14 (sCD14) in contrast to the response of colonic epithelial cells. (4) Water-soluble PGN, SEPS, prepared from Staphylococcus epidermidis activated cells in a TLR2-dependent manner. When the glycan chain of SEPS was cleaved enzymatically, the TLR2-dependent activity of SEPS disappeared, and MDP was also inactive in this respect. (5) MDP activated human monocytic cells in a CD14- and TLR2-independent manner and up-regulated expression of MyD88, resulting in synergistic activation of the cells in combination with LPS or LTA, both of which are TLR4-dependent activators. (6) Interferon-γ primed HGF to increase response to LPS through up-regulation of mCD14 and MyD88 mRNA expression. Further studies are in progress in our laboratory to identify interactions between bacterial components and the host innate immune system in relation to pathogenesis of periodontal diseases.

  46. 早期発症型歯周炎における顆粒球系生体防御機構の細胞・分子生物学的解析 Competitive

    根本 英二

    Offer Organization: 文部科学省

    System: 科学研究費補助金 奨励(A)

    1998/04 - 2000/03

  47. Candida albicansによるアナフィラキシー様急性炎症の惹起-細胞壁マンナンによるレクチン経路を介する補体活性化の可能性-

    高田 春比古, 根本 英二, 中村 雅典, 遠藤 康男

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 萌芽的研究

    Institution: 東北大学

    2000 - 2000

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    報告者らはこれまでに、i)歯周病関連細菌のLPS,口腔レンサ球菌ならびにCandida albicansより調製した細胞壁画分を、細菌細胞壁ペプチドグリカンの要構造に当たる合成ムラミルジペプチド(MDP)を前投与したマウスに静脈注射すると、アナフィラキシー様ショック反応を惹起すること、ii)LPSによるショック反応の背景には血小板の末梢血から肺等への急激な移行と、臓器での凝集・崩壊、それに続発する急性の組織破壊が起こっており、MDPはこのような血小板反応を増強すること、iii)さらに、一連の反応の成立には、補体が必須であることを明らかにしてきた。本研究の当初の計画では、マンナンを主要構成多糖とするC.albicansの細胞壁がmannose-binding lectin(MBL)と結合して、所謂レクチン経路を介する補体活性化を起こす結果、血小板崩壊に続発するアナフィラキシー様反応が起こるとの作業仮説の実証を目指していた。しかし、研究の途上で、マンノースホモポリマー(MHP)を保有するKlebsiella O3(KO3)のLPSに極めて強力なショック誘導作用を認めたので、先ず、MHP保有LPSを供試する実験を実施した。即ち、横地高志教授(愛知医大)より、KO3の他、E.coli O8とO9(いずれもMHPよりなるO多糖を保有)さらに、O8およびO9合成酵素をコードする遺伝子をE.coli K12(O多糖欠くR変異株)に導入して得た遺伝子組替えLPSの分与を受けて、MHP保有LPSが例外無く強力なショック反応と血小板反応を惹起すること、さらに、松下操博士(福島医大)の協力を得て、MHP保有LPSはヒトMBLと結合して、血清中のC4を捉えて、補体系を活性化することを証明した。

  48. Project study of host defense functions and periodontal tissue regenerations in cionic periodontal disease

    MAEDA Katsumasa, YOSHINO Hiroshi, YOSHIE Hiromasa, NEMOTO Eiji, HIRATA Masato, ISHIKAWA Isao

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (A).

    Institution: KYUSHU UNIVERSITY

    1998 - 2000

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    1. Analysis of host defense response in periodontal diseases. Periodontal diseases are initiated with infection of periodnotopathogenic bacteria in dental plaque. To elucidate the host defense response in the process of disease progression is deeply related with the understanding of the repair reaction in the process of healing from diseases. In this project, we scientifically revealed the role of neutrophils and fibroblasts which are the initial responders in the host defense mechanism. Furthermore, we analyzed the immune response with T-cells which play a central role in the host defense response and we obtained the following results. At the stage of immune response with Th-1 cells and macrophages, a strong bactericidal activity was exhibited, but on the other hand, periodontal tissues were destructed. The immune response with Th-1 cells has a variation among individuals, and it was speculated that this variation may bring about the difference of periodontal diseases among patients. 2. Analysis of tissue repair in periodontal diseases. We analyzed the hyaluronic acid in the healing process from injury, and we found that at this process, high MVV type hyaluronic acid was produced and it provided the mesenchymal cells with the base for growth and induced the tissue repair. It was also found that eight genes are functioning in the process of healing from injury. Furthermore, when we systemically administer prostaglandin, which is known to promote bone resorption, the bone resorption was found to be inhibited. When we apply the self-resolving membrane with tetracycline on GTR, the formation of new alveolar bone was increased. From these results, we obtained the basic information for the clue from the tissue repair to tissue regeneration.

  49. Bacterial cell surface amphiphiles and periodontal diseases - Study on the role of CD14 molecule in periodontal tissues -

    TAKADA Haruhiko, NEMOTO Eiji, SUGAWARA Shunji

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: TOHOKU UNIVERSITY

    1998 - 1999

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    Bacterial cell surface amphiphiles exhibit various biological activities. Endotoxic lipopolysaccharides (LPS) distributed in the outer membrane of gram-negative bacteria and lipoteichoic acid (LTA) distributed in the cell surfaces of gram-positive bacteria are representative bioactive amphiphiles. Bacterial amphiphiles activate host cells such as macrophages through membrane CD14 (mCD14) expressed on cell surfaces. Last year, we demonstrated the presence of two types of human gingival fibroblasts that highly and lowly express mCD14, and the former cells produced interleukin-8 (IL-8) upon stimulation with LPS and lipid A from Enterobacteriaceae. This year, we found that 1. Bacillus subtilis LTA also activated human gingival fibroblasts via mCD14, whereas LTA from oral streptococci such as Streptococcus sanguis and Streptococcus mutans acted as an LPS-antagonist to inhibit IL-8-induction by LPS. 2. The LPS fraction from Prevotella intermedia, periodontal disease-associated bacteria, activated human dental pulp cells that lack mCD14, in a soluble CD14- and nuclear factor AP-1-dependent manner. 3. Furthermore, in collaboration with Prof. Shizuo Akira, Osaka University, we studied the relationship between amphiphiles and the Toll-like receptor (TLR) system, which was recently revealed to be associated with CD14 and is involved in LPS signaling. We revealed that LTA as well as LPS was recognized by TLR4 in contrast to previous reports. We also obtained evidence suggesting that a bioactive glycoprotein, PGP, prepared from P. intermedia, was recognized by TLR2. With the viewpoint that "bacterial products overstimulate the innate immune system, and result in tissue destruction," we would like to reveal how the CD14/TLR system recognizes and responds to microbes in periodontal tissues in relation to the pathogenesis of periodontal diseases.

  50. 黒色色素産生菌LPSによるアナフィラキシー様急性炎症の惹起

    高田 春比古, 根本 英二, 中村 雅典, 遠藤 康男

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 萌芽的研究

    Institution: 東北大学

    1998 - 1998

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    先に申請者らは、歯周病に深く係わるとされるPorphyromonas gingivalis,Prevotella intermedia等の黒色色素産生菌(BPB)のリポ多糖(LPS)をマウスに静脈注射すると、通常のLPSでは報告のない全身アナフィラキシー様反応を惹起する事を見出した。さらに、この反応の背景には血小板の末梢血から肺・肝等への急激な移行と、臓器での凝集・崩壊、それに続発する急性の組織破壊が起こる事を明らかにした。これらの反応の機序解明を目指して、補体系との係わりに焦点を絞って研究した。研究にあたっては、アナフィラキシー様反応惹起能が強いKlebsiella 03(K03)のLPS(愛知医大・横地高志教授より分与を受けた)を主として供試した。その結果、1.先天的に補体因子C5を欠くDBA/2マウスやAKRマウスではアナフィラキシー様反応や血小板の崩壊が起こらない。2.C5抑制剤K-75 COOHを予め投与されたマウスやコブラ毒素を投与して補体を枯渇させたマウスでも、アナフィラキシー様反応や血小板崩壊が起こらない。3.補体活性化作用が弱いKO3変異株のLPSでは、血小板の一過性の肺・肝への移行はみられるが、やがて血液に戻り、アナフィラキシー様反応も認められない。これらの知見はLPSによって惹起される血小板-アナフィラキシー様反応には補体活性化が必須がであることを示唆している。報告者は、K03 LPSの0多糖部のマンノースホモポリマー(MHP)がレクチン経路(近年解明された第3の補体活性化経路)を介して補体を強力に活性化して、集積した血小板を崩壊させ、アナフィラキシー様反応を惹起するとの作業仮説を立てた。実際、4.Esherichia coli 0111:B4にMHP合成遺伝子を導入した変異株のLPS(横地教授より分与)では、親株のLPSに認められない強力な血小板反応とアナフィラキシー様反応惹起作用が認められた。今後、歯周局所でもBPB LPSによって、同様の機序による急性炎症が惹起されている可能性を探究する予定である。

  51. Discrimination between Cementoblast and Odontoblast using the Immunological Surface Marker

    SHOJI Shigeru, NEMOTO Eiji, IIYAMA Masao, HORIUCHI Hiroshi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: TOHOKU UNIVERSITY

    1997 - 1998

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    To regenerate the periodontal tissue, many researches have been done. The guided tissue regeneration method attaches the membrane to a root, and makes the regenerationspace for cementum, periodontal ligament and alveolar bone. Recently the enamel protein(amelogenin), which is extracted from pig toothgerm, is applied to induce the cementoblast. In 1997 we thought that the cementoblast secrete non-collagenous protein (osteopontin, sialoprotein ). So if we found the cells near the non-collagenous protein stained byimmuno-histochemical technique, we thought those cells were cementoblast. But it was very difficult to determine the cells only by their position. In 1998 we fixed our eyes on Hertwig's epithelial sheath. At the position of the formation of tooth root, a mass of Hertwigh's epithelial cells contacts with the mesenchymal cells through the laminin. We thought these mesenchymal cells, whose have a vitamin D3receptor, were cementoblast. The observation using translating electron microscopy showed the cells contacted with Hertwig's epithelial cells, and that these cells secreted the alkalinephosphatase. But we could not find the vitamin D3 receptor on these cells. We should reconsider the criteria of cementoblast, and pay the attention to the difference of cementum between human and rat.

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