Details of the Researcher

PHOTO

Masahiro Saito
Section
Graduate School of Dentistry
Job title
Professor
Degree

  • 博士（歯学）（神奈川歯科大学）

Research Areas 1

  • Life sciences / Conservative dentistry and endodontics /

Papers 91

  1. Irrigation with reduced sodium hypochlorite solution concentration using laser-induced cavitation is effective and safe in rat intraradicular biofilm model. International-journal

    Takehiro Uematsu, Yoshio Yahata, Koyuki Ohnishi, Shigeto Suzuki, Masafumi Kanehira, Toshinori Tanaka, Susumu Sudo, Venkata Venkataiah Suresh, Masahiro Saito

    Australian endodontic journal : the journal of the Australian Society of Endodontology Inc　49　(3)　544-553　2023/12

    DOI： 10.1111/aej.12783 　

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    This study aimed to investigate the optimal sodium hypochlorite solution (NaOCl) concentration to effectively remove the root canal biofilm without stimulating periradicular inflammation using coronal laser-activated irrigation (CLAI). To compare the efficacy of different NaOCl concentrations combined with CLAI in removing the biofilm, an in vivo intraradicular biofilm rat model was used. Root canals were irrigated using an Er:YAG laser with either 5% or 0.5% NaOCl. Biofilm removal efficacy of CLAI was compared to that of conventional needle irrigation using scanning electron microscopy (SEM) and quantitative polymerase chain reaction (qPCR). Histological observation of CLAI-associated periradicular inflammation was also conducted. In both the 5% and 0.5% CLAI groups, SEM observation showed the opening of the dentin tubules and biofilm removal. qPCR analysis indicated that the residual bacteria counts after cleaning were significantly lower in the 5% and 0.5% CLAI groups than in the conventional needle irrigation and positive control groups (Tukey test, p < 0.05), and no significant difference was observed between the 5% and 0.5% CLAI groups (p > 0.05). Periapical inflammation in the 5% CLAI group revealed the most severe, including significant neutrophilic and lymphocytic infiltration with abscess formation, while only mild vasodilation was observed in the 0.5% CLAI group. CLAI can remove the biofilm independently of chemical action, which avoids the risks associated with high NaOCl concentrations. Therefore, this root canal irrigation technique ensures safety and effectiveness, promising to contribute to new treatment strategies intended to remove intraradicular biofilm.

  2. 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

  3. 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

  4. Correction of large jawbone defect in the mouse using immature osteoblast-like cells and a 3D polylactic acid scaffold. International-journal

    Shigeto Suzuki, Venkata Suresh Venkataiah, Yoshio Yahata, Akira Kitagawa, Masahiko Inagaki, Mary M Njuguna, Risako Nozawa, Yusuke Kakiuchi, Masato Nakano, Keisuke Handa, Masahiro Yamada, Hiroshi Egusa, Masahiro Saito

    PNAS nexus　1　(4)　pgac151　2022/09

    DOI： 10.1093/pnasnexus/pgac151 　

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    Bone tissue engineering has been developed using a combination of mesenchymal stem cells (MSCs) and calcium phosphate-based scaffolds. However, these complexes cannot regenerate large jawbone defects. To overcome this limitation of MSCs and ceramic scaffolds, a novel bone regeneration technology must be developed using cells possessing high bone forming ability and a scaffold that provides space for vertical bone augmentation. To approach this problem in our study, we developed alveolar bone-derived immature osteoblast-like cells (HAOBs), which have the bone regenerative capacity to correct a large bone defect when used as a grafting material in combination with polylactic acid fibers that organize the 3D structure and increase the strength of the scaffold material (3DPL). HAOB-3DPL constructs could not regenerate bone via xenogeneic transplantation in a micromini pig alveolar bone defect model. However, the autogenic transplantation of mouse calvaria-derived immature osteoblast-like cells (MCOBs) isolated using the identical protocol for HAOBs and mixed with 3DPL scaffolds successfully regenerated the bone in a large jawbone defect mouse model, compared to the 3DPL scaffold alone. Nanoindentation analysis indicated that the regenerated bone had a similar micromechanical strength to native bone. In addition, this MCOB-3DPL regenerated bone possesses osseointegration ability wherein a direct structural connection is established with the titanium implant surface. Hence, a complex formed between a 3DPL scaffold and immature osteoblast-like cells such as MCOBs represents a novel bone tissue engineering approach that enables the formation of vertical bone with the micromechanical properties required to treat large bone defects.

  5. 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

  6. 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

  7. 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

  8. 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

  9. Er:YAG laser-induced cavitation can activate irrigation for the removal of intraradicular biofilm. International-journal

    Taiji Nagahashi, Yoshio Yahata, Keisuke Handa, Masato Nakano, Shigeto Suzuki, Yusuke Kakiuchi, Toshinori Tanaka, Masafumi Kanehira, Venkata Suresh Venkataiah, Masahiro Saito

    Scientific reports　12　(1)　4897-4897　2022/03/22

    DOI： 10.1038/s41598-022-08963-x 　

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    We investigated the biofilm removal effects of laser activated irrigation (LAI) using a pig model, focusing on the impact of the fiber tip position, and used a high-speed camera to observe the occurrence and positioning of the cavitation associated with laser irradiation. A total of 16 roots of deciduous mandibular second premolars from 4 pigs were used. After a pulpectomy, the canals were left open for 2 weeks and sealed for 4 weeks to induce intraradicular biofilm. Root canal irrigation was then performed with Er:YAG laser activation. The fiber tip was inserted at two different positions, i.e., into the root canal in the intracanal LAI group and into the pulp chamber in the coronal LAI group. Intracanal needle irrigation with saline or 5% NaOCl was utilized in the positive control and conventional needle irrigation (CNI) groups. SEM and qPCR were carried out to evaluate treatment efficacy. Statistical analysis was performed using ANOVA and a Tukey-Kramer post-hoc test for qPCR and with a Steel-Dwass test to compare the SEM scores, with α = 0.05. A high-speed camera was used to observe the generation of cavitation bubbles and the movement of the induced bubbles after laser irradiation. The intracanal and coronal LAI groups showed significantly lower amounts of bacteria than either the positive control or CNI groups. There was no significant difference found between the intracanal and coronal LAI groups. SEM images revealed opened dentinal tubules with the destruction of biofilm in both LAI groups. High-speed camera images demonstrated cavitation bubble production inside the root canal after a single pulse irradiation pulse. The generated bubbles moved throughout the entire internal multi-rooted tooth space. Coronal LAI can generate cavitation in the root canal with a simply placed fiber inside the pulp chamber, leading to effective biofilm removal. This method could thus contribute to the future development of endodontic treatments for refractory apical periodontitis caused by intraradicular biofilm.

  10. An experimental intraradicular biofilm model in the pig for evaluating irrigation techniques

    Toshinori Tanaka, Yoshio Yahata, Keisuke Handa, Suresh V. Venkataiah, Mary M. Njuguna, Masafumi Kanehira, Tatsuya Hasegawa, Yuichiro Noiri, Masahiro Saito

    BMC Oral Health　21　(1)　2021/12

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1186/s12903-021-01536-w 　

    eISSN： 1472-6831

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    <title>Abstract</title><sec> <title>Background</title> We established an in vivo intraradicular biofilm model of apical periodontitis in pigs in which we compared the efficacy of different irrigant activation techniques for biofilm removal. </sec><sec> <title>Methods</title> Twenty roots from the deciduous mandibular second premolar of 5 male pigs were used. After pulpectomy, canals were left open for 2 weeks and then sealed for 4 weeks to enable the development of an intracanal biofilm. The intraradicular biofilms was evaluated using SEM and bacterial 16S rRNA gene-sequencing. To investigate the efficacy of biofilm removal, root canal irrigations were performed using conventional needle, passive ultrasonic, subsonic, or laser-activated irrigation. Real-time PCR was conducted to quantitate the remaining biofilm components. Statistical analysis was performed using ANOVA followed by a <italic>Tukey kramer</italic> post-hoc test with α = 0.05. </sec><sec> <title>Results</title> The pulp exposure model was effective in inducing apical periodontitis and SEM analysis revealed a multi-layer biofilm formation inside the root canal. 16S rRNA sequence analysis identified Firmicutes, Bacteroidetes, and Fusobacteria as the predominant bacterial phyla components, which is similar to the microbiome profile seen in humans. None of the tested irrigation techniques completely eradicated the biofilm components from the root canal, but the subsonic and laser-activated irrigation methods produced the lowest bacterial counts (<italic>p</italic> &lt; 0.05). </sec><sec> <title>Conclusions</title> An experimental intraradicular biofilm model has been successfully established in pigs. Within the limitations of the study, subsonic or laser-activated irrigation demonstrated the best biofilm removal results in the pig system. </sec>

  11. Clinical Applications of Cell-Scaffold Constructs for Bone Regeneration Therapy. International-journal

    Venkata Suresh Venkataiah, Yoshio Yahata, Akira Kitagawa, Masahiko Inagaki, Yusuke Kakiuchi, Masato Nakano, Shigeto Suzuki, Keisuke Handa, Masahiro Saito

    Cells　10　(10)　2021/10/08

    DOI： 10.3390/cells10102687 　

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    Bone tissue engineering (BTE) is a process of combining live osteoblast progenitors with a biocompatible scaffold to produce a biological substitute that can integrate into host bone tissue and recover its function. Mesenchymal stem cells (MSCs) are the most researched post-natal stem cells because they have self-renewal properties and a multi-differentiation capacity that can give rise to various cell lineages, including osteoblasts. BTE technology utilizes a combination of MSCs and biodegradable scaffold material, which provides a suitable environment for functional bone recovery and has been developed as a therapeutic approach to bone regeneration. Although prior clinical trials of BTE approaches have shown promising results, the regeneration of large bone defects is still an unmet medical need in patients that have suffered a significant loss of bone function. In this present review, we discuss the osteogenic potential of MSCs in bone tissue engineering and propose the use of immature osteoblasts, which can differentiate into osteoblasts upon transplantation, as an alternative cell source for regeneration in large bone defects.

  12. 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.

  13. めざせ!エンドエキスパートへの道 クロノロジカルに学ぼう!進化するニッケルチタンファイル

    八幡 祥生, 齋藤 正寛

    DENTAL DIAMOND　45　(12)　70-75　2020/09

    Publisher: (株)デンタルダイヤモンド社

    ISSN： 0386-2305

  14. in vivo感染根管モデルを用いたEr:YAGレーザーの洗浄効果

    長橋 泰次, 半田 慶介, 兼平 正史, 八幡 祥生, 田中 利典, 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　152回　40-40　2020/06

    Publisher: (NPO)日本歯科保存学会

  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, 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

  16. 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

  17. ヒト抜去歯象牙質における液透過性の定量的計測

    石幡 浩志, 兼平 正史, 齋藤 正寛, 山田 聡, 小山 二三夫

    生体医歯工学共同研究拠点成果報告書　令和元年度　157-157　2020/04

    Publisher: 東京医科歯科大学生体材料工学研究所

  18. ヒト抜去歯象牙質における液透過性の定量的計測

    石幡 浩志, 兼平 正史, 齋藤 正寛, 山田 聡, 小山 二三夫

    生体医歯工学共同研究拠点成果報告書　令和元年度　157-157　2020/04

    Publisher: 東京医科歯科大学生体材料工学研究所

  19. 歯根尖切除術の教育用顎模型システムの開発とその評価

    高見澤 哲矢, 半田 慶介, 鈴木 重人, 長谷川 達也, 中野 将人, 八幡 祥生, 齋藤 正寛

    日本歯科保存学雑誌　63　(2)　188-198　2020/04

    Publisher: (NPO)日本歯科保存学会

    ISSN： 0387-2343

    eISSN： 2188-0808

  20. Comparison of the vertical bone defect healing abilities of carbonate apatite, β-tricalcium phosphate, hydroxyapatite and bovine-derived heterogeneous bone.

    Nobuya Sato, Keisuke Handa, Venkata Suresh Venkataiah, Tatsuya Hasegawa, Mary M Njuguna, Yoshio Yahata, Masahiro Saito

    Dental materials journal　39　(2)　309-318　2020/03/31

    DOI： 10.4012/dmj.2019-084 　

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    The treatment of vertical bone defects caused by severe periodontal disease requires the regeneration of periodontal tissue. Although various bone substitutes have been clinically applied to vertical bone defect correction, the evaluation of these materials in periodontal tissue remains incomplete. The purpose of this study was to examine the bone regeneration abilities of various bone substitutes including Cytrans, Cerasorb, Neobone and Bio-Oss in a 3-wall bone defect animal model. All of these bone substitutes showed a similar healing ability to periodontal ligament and cementum. However, Cytrans showed the fastest bone healing ability compared with the other materials at 4 weeks post-transplantation. In addition, the recruitment of osteoclasts and endothelial cells was observed in Cytrans grafts at 4 weeks, but only detected at 8 weeks in the other materials. These results suggest that Cytrans promotes faster bone healing by inducing bone remodeling and angiogenesis.

  21. 根尖性歯周炎の免疫学と治療抵抗性に対する新規歯内療法開発への課題

    長谷川 達也, 中野 将人, 鈴木 重人, 半田 慶介, 八幡 祥生, 佐藤 暢也, 齋藤 正寛

    日本歯内療法学会雑誌　41　(1)　8-15　2020/01

    Publisher: 日本歯内療法学会

    ISSN： 1347-8672

    eISSN： 2423-9429

  22. 臨床応用を目指した歯槽骨由来未分化前骨芽細胞の分離培養システム構築

    鈴木 重人, Njuguna Mary M., Venkataiah Suresh V., 中野 将人, 八幡 祥生, 半田 慶介, 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　151回　24-24　2019/10

    Publisher: (NPO)日本歯科保存学会

  23. 未分化骨芽細胞と3次元ポリ乳酸複合体を用いた歯槽骨再生医療の開発

    八幡 祥生, 鈴木 重人, Njuguna Mary M., Venkataiah Suresh V., 半田 慶介, 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　151回　31-31　2019/10

    Publisher: (NPO)日本歯科保存学会

  24. 根尖性歯周炎の病因・病態に基づいた新規治療戦略の開発

    長谷川 達也, 半田 慶介, 八幡 祥生, 田中 利典, 中野 将人, 野杁 由一郎, 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　151回　55-55　2019/10

    Publisher: (NPO)日本歯科保存学会

  25. 消毒剤がケイ酸カルシウム系セメント表面硬度に与える影響

    須藤 享, 半田 慶介, 兼平 正史, 八幡 祥生, 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　150回　38-38　2019/05

    Publisher: (NPO)日本歯科保存学会

  26. 歯根端切除術の教育を目的とした顎模型システムの開発とその評価

    高見澤 哲矢, 鈴木 重人, 長谷川 達也, 佐藤 暢也, 八幡 祥生, 半田 慶介, 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　150回　42-42　2019/05

    Publisher: (NPO)日本歯科保存学会

  27. 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

    Wang Z, Maruyama K, Sakisaka Y, Suzuki S, Tada H, Suto M, Saito M, Yamada S, Nemoto E

    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.

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

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

    Scientific reports　9　(1)　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.

  29. ラット露髄歯におけるPituitary adenylate cyclase-activating polypeptideの分布

    矢島 健大, 佐藤 匡, 齋藤 正寛, 市川 博之

    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　108-108　2018/10

    Publisher: (NPO)日本歯科保存学会

  30. Fibrillin-1 insufficiency alters periodontal wound healing failure in a mouse model of Marfan syndrome Peer-reviewed

    Keisuke Handa, Syouta Abe, V. Venkata Suresh, Yoshiyasu Fujieda, Masaki Ishikawa, Ai Orimoto, Yoko Kobayashi, Satoru Yamada, Satoko Yamaba, Shinya Murakami, Masahiro Saito

    Archives of Oral Biology　90　53-60　2018/06/01

    Publisher: Elsevier Ltd

    DOI： 10.1016/j.archoralbio.2018.02.017 　

    ISSN： 1879-1506 0003-9969

    eISSN： 1879-1506

  31. 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.

  32. F-spondin negatively regulates dental follicle differentiation through the inhibition of TGF-beta activity Peer-reviewed

    Ai Orimoto, Misaki Kurokawa, Keisuke Handa, Masaki Ishikawa, Eisaku Nishida, Makoto Aino, Akio Mitani, Miho Ogawa, Takashi Tsuji, Masahiro Saito

    ARCHIVES OF ORAL BIOLOGY　79　7-13　2017/07

    DOI： 10.1016/j.archoralbio.2017.02.019 　

    ISSN： 0003-9969

    eISSN： 1879-1506

  33. Pannexin 3 regulates proliferation and differentiation of odontoblasts via its hemichannel activities Peer-reviewed

    Tsutomu Iwamoto, Takashi Nakamura, Masaki Ishikawa, Keigo Yoshizaki, Asuna Sugimoto, Hiroko Ida-Yonemochi, Hayato Ohshima, Masahiro Saito, Yoshihiko Yamada, Satoshi Fukumoto

    PLOS ONE　12　(5)　e0177557　2017/05

    DOI： 10.1371/journal.pone.0177557 　

    ISSN： 1932-6203

  34. Metal ions from S-PRG filler have the potential to prevent periodontal disease Peer-reviewed

    Yoko Iwamatsu-Kobayashi, Syouta Abe, Yoshiyasu Fujieda, Ai Orimoto, Masafumi Kanehira, Keisuke Handa, Venkata Suresh Venkataiah, Wei Zou, Masaki Ishikawa, Masahiro Saito

    Clinical and Experimental Dental Research　3　(4)　126-133　2017

    Publisher: Wiley-Blackwell

    DOI： 10.1002/cre2.70 　

    ISSN： 2057-4347

  35. Generation of heterozygous fibrillin-1 mutant cloned pigs from genome-edited foetal fibroblasts Peer-reviewed

    Kazuhiro Umeyama, Kota Watanabe, Masahito Watanabe, Keisuke Horiuchi, Kazuaki Nakano, Masateru Kitashiro, Hitomi Matsunari, Tokuhiro Kimura, Yoshimi Arima, Oltea Sampetrean, Masaki Nagaya, Masahiro Saito, Hideyuki Saya, Kenjiro Kosaki, Hiroshi Nagashima, Morio Matsumoto

    SCIENTIFIC REPORTS　6　24413　2016/04

    DOI： 10.1038/srep24413 　

    ISSN： 2045-2322

  36. ラット口腔顔面領域におけるTRPM8陽性神経線維の分布

    矢島 健大, 佐藤 匡, 市川 博之, 齋藤 正寛, 島内 英俊, 細川 浩, 近藤 照義

    Journal of Oral Biosciences Supplement　2015　159-159　2015/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  37. ラット口腔顔面領域におけるTRPM8陽性神経線維の分布

    矢島 健大, 佐藤 匡, 市川 博之, 齋藤 正寛, 島内 英俊, 細川 浩, 近藤 照義

    Journal of Oral Biosciences Supplement　2015　253-253　2015/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  38. Periostin is a negative regulator of mineralization in the dental pulp tissue Peer-reviewed

    Mengu Zhou, Nobuyuki Kawashima, Noriyuki Suzuk, Mioko Yamamoto, Kayoko Ohnishi, Ken-ichi Katsube, Hideyuki Tanabe, Akira Kudo, Masahiro Saito, Hideaki Suda

    ODONTOLOGY　103　(2)　152-159　2015/05

    DOI： 10.1007/s10266-014-0152-7 　

    ISSN： 1618-1247

    eISSN： 1618-1255

  39. Interaction between Fibronectin and beta 1 Integrin Is Essential for Tooth Development Peer-reviewed

    Kan Saito, Emiko Fukumoto, Aya Yamada, Kenji Yuasa, Keigo Yoshizaki, Tsutomu Iwamoto, Masahiro Saito, Takashi Nakamura, Satoshi Fukumoto

    PLOS ONE　10　(4)　e0121667　2015/04

    DOI： 10.1371/journal.pone.0121667 　

    ISSN： 1932-6203

  40. Isolation and characterization of the human immature osteoblast culture system from the alveolar bones of aged donors for bone regeneration therapy Peer-reviewed

    Makoto Aino, Eisaku Nishida, Yoshiyasu Fujieda, Ai Orimoto, Akio Mitani, Toshihide Noguchi, Hatsune Makino, Shinya Murakami, Akihiro Umezawa, Toshiyuki Yoneda, Masahiro Saito

    EXPERT OPINION ON BIOLOGICAL THERAPY　14　(12)　1731-1744　2014/12

    DOI： 10.1517/14712598.2014.960387 　

    ISSN： 1471-2598

    eISSN： 1744-7682

  41. Functional tooth restoration by next-generation bio-hybrid implant as a bio-hybrid artificial organ replacement therapy. International-journal Peer-reviewed

    Masamitsu Oshima, Kaoru Inoue, Kei Nakajima, Tetsuhiko Tachikawa, Hiromichi Yamazaki, Tomohide Isobe, Ayaka Sugawara, Miho Ogawa, Chie Tanaka, Masahiro Saito, Shohei Kasugai, Teruko Takano-Yamamoto, Takashi Inoue, Katsunari Tezuka, Takuo Kuboki, Akira Yamaguchi, Takashi Tsuji

    Scientific reports　4　6044-6044　2014/08/13

    DOI： 10.1038/srep06044 　

    More details Close

    Bio-hybrid artificial organs are an attractive concept to restore organ function through precise biological cooperation with surrounding tissues in vivo. However, in bio-hybrid artificial organs, an artificial organ with fibrous connective tissues, including muscles, tendons and ligaments, has not been developed. Here, we have enveloped with embryonic dental follicle tissue around a HA-coated dental implant, and transplanted into the lower first molar region of a murine tooth-loss model. We successfully developed a novel fibrous connected tooth implant using a HA-coated dental implant and dental follicle stem cells as a bio-hybrid organ. This bio-hybrid implant restored physiological functions, including bone remodelling, regeneration of severe bone-defect and responsiveness to noxious stimuli, through regeneration with periodontal tissues, such as periodontal ligament and cementum. Thus, this study represents the potential for a next-generation bio-hybrid implant for tooth loss as a future bio-hybrid artificial organ replacement therapy.

  42. Three-dimensional spheroid culture promotes odonto/osteoblastic differentiation of dental pulp cells Peer-reviewed

    Mioko Yamamoto, Nobuyuki Kawashima, Nami Takashino, Yu Koizumi, Koyo Takimoto, Noriyuki Suzuki, Masahiro Saito, Hideaki Suda

    ARCHIVES OF ORAL BIOLOGY　59　(3)　310-317　2014/03

    DOI： 10.1016/j.archoralbio.2013.12.006 　

    ISSN： 0003-9969

    eISSN： 1879-1506

  43. 歯周組織を有する新規機能性インプラントの開発

    大島 正充, 井上 香織, 中島 啓, 小川 美帆, 山本 照子, 井上 孝, 立川 哲彦, 春日井 昇平, 齋藤 正寛, 窪木 拓男, 辻 孝

    岡山歯学会雑誌　32　(2)　90-90　2013/12

    Publisher: 岡山歯学会

    ISSN： 0913-3941

  44. ラット三叉神経節におけるendomorphin-1の分布 免疫組織化学的手法による検討

    矢島 健大, 佐藤 匡, 齋藤 正寛, 市川 博之

    Journal of Oral Biosciences Supplement　2013　147-147　2013/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  45. Wnt11 expression in rat dental pulp and promotional effects of Wnt signaling on odontoblast differentiation Peer-reviewed

    Yu Koizumi, Nobuyuki Kawashima, Mioko Yamamoto, Koyo Takimoto, Mengyu Zhou, Noriyuki Suzuki, Masahiro Saito, Hidemitsu Harada, Hideaki Suda

    CONGENITAL ANOMALIES　53　(3)　101-108　2013/09

    DOI： 10.1111/cga.12011 　

    ISSN： 0914-3505

  46. Gadd45g regulates dental epithelial cell proliferation through p38 MAPK-mediated p21 expression Peer-reviewed

    Kentaro Ishida, Yohei Yuge, Mai Hanaoka, Masato Yasukawa, Yoko Minami, Miho Ogawa, Ko-hei Masumoto, Yasufumi Shigeyoshi, Masahiro Saito, Takashi Tsuji

    GENES TO CELLS　18　(8)　660-671　2013/08

    DOI： 10.1111/gtc.12067 　

    ISSN： 1356-9597

  47. Dpysl4 Is Involved in Tooth Germ Morphogenesis through Growth Regulation, Polarization and Differentiation of Dental Epithelial Cells Peer-reviewed

    Masato Yasukawa, Kentaro Ishida, Yohei Yuge, Mai Hanaoka, Yoko Minami, Miho Ogawa, Takashi Sasaki, Masahiro Saito, Takashi Tsuji

    INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES　9　(4)　382-390　2013

    DOI： 10.7150/ijbs.5510 　

    ISSN： 1449-2288

  48. Effects of MMP-3 on Inflammatory Mediator Synthesis under LPS Stimulation

    瀧本晃陽, 川島伸之, 鈴木規元, 小泉悠, 山本弥生子, 齋藤正寛, 原田英光, 中島美砂子, 須田英明

    日本歯科保存学雑誌　55　(3)　202-210　2012/06/30

    Publisher: The Japanese Society of Conservative Dentistry

    DOI： 10.11471/shikahozon.55.202 　

    ISSN： 0387-2343

    More details Close

    Purpose: Matrix metalloproteinase (MMP)-3 is a member of the MMP family, which comprises typical proteinases that degrade the extracellular matrix. MMP-3 is involved in various physiological and pathological processes. Recently, application of MMP-3 to injured pulp tissues was reported to induce angiogenesis and wound healing, but its anti-inflammatory functions are still unknown. The purposes of this study were to evaluate the effects of MMP-3 on inflammatory mediator synthesis from macrophages (RAW264) and mice dental papilla cells (MDP). Methods: RAW264 and MDP were cultured in 10% FBS supplemented D-MEM and MEMα, respectively. They were stimulated by LPS (100 ng/ml) in the presence or absence of MMP-3 (100 ng/ml) Non-LPS-stimulated RAW264 and MDP were used as controls. NO production was measured using the Griess reagent, and inflammatory mediator synthesis was evaluated using real-time PCR. Effects of MMP-3 for cell growth and caspase-3 activity were assessed. Results: Application of MMP-3 down-regulated the NO synthesis from LPS-stimulated macrophages, which showed a typical increase of NO synthesis compared to non-LPS-stimulated macrophages. mRNA of inflammatory mediators (IL-1β, IL-6, TNF-α and Cox2) was highly expressed in LPS-stimulated macrophages, but the application of MMP-3 significantly down-regulated their expression. Cox2 mRNA expression was highly induced in LPS-stimulated MDP, which was down-regulated by MMP-3 application. MMP-3 did not influence the cell growth and caspase-3 activity of RAW264 and MDP. Conclusion: MMP-3 down-regulated the inflammatory-mediator synthesis from LPS-stimulated macrophages and dental papilla cells, suggesting that MMP-3 may be a candidate for reducing pulpal inflammation.

  49. Roles of Heparan Sulfate Sulfation in Dentinogenesis Peer-reviewed

    Satoru Hayano, Hiroshi Kurosaka, Takeshi Yanagita, Ina Kalus, Fabian Milz, Yoshihito Ishihara, Md. Nurul Islam, Noriaki Kawanabe, Masahiro Saito, Hiroshi Kamioka, Taiji Adachi, Thomas Dierks, Takashi Yamashiro

    JOURNAL OF BIOLOGICAL CHEMISTRY　287　(15)　12217-12229　2012/04

    DOI： 10.1074/jbc.M111.332924 　

    ISSN： 0021-9258

  50. Role of Epithelial-Stem Cell Interactions during Dental Cell Differentiation Peer-reviewed

    Makiko Arakaki, Masaki Ishikawa, Takashi Nakamura, Tsutomu Iwamoto, Aya Yamada, Emiko Fukumoto, Masahiro Saito, Keishi Otsu, Hidemitsu Harada, Yoshihiko Yamada, Satoshi Fukumoto

    JOURNAL OF BIOLOGICAL CHEMISTRY　287　(13)　10590-10601　2012/03

    DOI： 10.1074/jbc.M111.285874 　

    ISSN： 0021-9258

    eISSN： 1083-351X

  51. Extracellular matrix administration as a potential therapeutic strategy for periodontal ligament regeneration Peer-reviewed

    Masahiro Saito, Takashi Tsuji

    EXPERT OPINION ON BIOLOGICAL THERAPY　12　(3)　299-309　2012/03

    DOI： 10.1517/14712598.2012.655267 　

    ISSN： 1471-2598

    eISSN： 1744-7682

  52. [Molecular mechanisms for the improvement of wound healing ability of periodontal ligament in Marfan's syndrome]. Peer-reviewed

    Saito M, Tsuji T

    Clinical calcium　22　(1)　35-42　2012/01

    ISSN： 0917-5857

  53. ADAMTSL6 beta Protein Rescues Fibrillin-1 Microfibril Disorder in a Marfan Syndrome Mouse Model through the Promotion of Fibrillin-1 Assembly Peer-reviewed

    Masahiro Saito, Misaki Kurokawa, Masahito Oda, Masamitsu Oshima, Ko Tsutsui, Kazutaka Kosaka, Kazuhisa Nakao, Miho Ogawa, Ri-ichiroh Manabe, Naoto Suda, Ganburged Ganjargal, Yasunobu Hada, Toshihide Noguchi, Toshio Teranaka, Kiyotoshi Sekiguchi, Toshiyuki Yoneda, Takashi Tsuji

    JOURNAL OF BIOLOGICAL CHEMISTRY　286　(44)　38602-38613　2011/11

    DOI： 10.1074/jbc.M111.243451 　

    ISSN： 0021-9258

  54. Induction of insulin-like growth factor 2 expression in a mesenchymal cell line co-cultured with an ameloblast cell line Peer-reviewed

    Asako Matsumoto, Hidemitsu Harada, Masahiro Saito, Akiyoshi Taniguchi

    IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL　47　(9)　675-680　2011/10

    DOI： 10.1007/s11626-011-9456-x 　

    ISSN： 1071-2690

  55. Functional Tooth Regeneration Using a Bioengineered Tooth Unit as a Mature Organ Replacement Regenerative Therapy Peer-reviewed

    Masamitsu Oshima, Mitsumasa Mizuno, Aya Imamura, Miho Ogawa, Masato Yasukawa, Hiromichi Yamazaki, Ritsuko Morita, Etsuko Ikeda, Kazuhisa Nakao, Teruko Takano-Yamamoto, Shohei Kasugai, Masahiro Saito, Takashi Tsuji

    PLOS ONE　6　(7)　e21531　2011/07

    DOI： 10.1371/journal.pone.0021531 　

    ISSN： 1932-6203

  56. Induction of enamel matrix protein expression in an ameloblast cell line co-cultured with a mesenchymal cell line in vitro Peer-reviewed

    Asako Matsumoto, Hidemitsu Harada, Masahiro Saito, Akiyoshi Taniguchi

    IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL　47　(1)　39-44　2011/01

    DOI： 10.1007/s11626-010-9362-7 　

    ISSN： 1071-2690

  57. ヘパラン硫酸の糖残基修飾は象牙質形成に関与する

    早野 暁, 黒坂 寛, 齋藤 正寛, 山城 隆

    Journal of Oral Biosciences　52　(Suppl)　119-119　2010/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

    eISSN： 1880-3865

  58. 歯小嚢に特異的に発現するF-spondinは歯根膜前駆細胞の分化を抑制する

    本間 宏実, 齋藤 正寛, 大嶋 隆, 米田 俊之

    Journal of Oral Biosciences　52　(Suppl)　123-123　2010/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

    eISSN： 1880-3865

  59. Dilated capillaries, disorganized collagen fibers and differential gene expression in periodontal ligaments of hypomorphic fibrillin-1 mice Peer-reviewed

    Ganjargal Ganburged, Naoto Suda, Masahiro Saito, Yosuke Yamazaki, Keitaro Isokawa, Keiji Moriyama

    CELL AND TISSUE RESEARCH　341　(3)　381-395　2010/09

    DOI： 10.1007/s00441-010-1021-5 　

    ISSN： 0302-766X

  60. Regulation of endoplasmic reticulum stress response by a BBF2H7-mediated Sec23a pathway is essential for chondrogenesis Peer-reviewed

    Atsushi Saito, Shin-ichiro Hino, Tomohiko Murakami, Soshi Kanemoto, Shinichi Kondo, Masahiro Saito, Riko Nishimura, Toshiyuki Yoneda, Tatsuya Furuichi, Shiro Ikegawa, Masahito Ikawa, Masaru Okabe, Kazunori Imaizumi

    NATURE CELL BIOLOGY　11　(10)　1197-U73　2009/10

    DOI： 10.1038/ncb1962 　

    ISSN： 1465-7392

    eISSN： 1476-4679

  61. Signalling mediated by the endoplasmic reticulum stress transducer OASIS is involved in bone formation Peer-reviewed

    Tomohiko Murakami, Atsushi Saito, Shin-ichiro Hino, Shinichi Kondo, Soshi Kanemoto, Kazuyasu Chihara, Hiroshi Sekiya, Kenji Tsumagari, Kimiko Ochiai, Kazuya Yoshinaga, Masahiro Saito, Riko Nishimura, Toshiyuki Yoneda, Ikuyo Kou, Tatsuya Furuichi, Shiro Ikegawa, Masahito Ikawa, Masaru Okabe, Akio Wanaka, Kazunori Imaizumi

    NATURE CELL BIOLOGY　11　(10)　1205-U90　2009/10

    DOI： 10.1038/ncb1963 　

    ISSN： 1465-7392

    eISSN： 1476-4679

  62. 歯根膜発生過程におけるF-spondinの機能解析

    本間 宏実, 齋藤 正寛, 大嶋 隆, 米田 俊之

    Journal of Oral Biosciences　51　(Suppl.)　101-101　2009/08

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

    eISSN： 1880-3865

  63. エナメル芽細胞分化過程における細胞間結合の役割

    山田亜矢, 岩本勉, 鈴木宏治, 中村卓史, 原田英光, 斎藤正寛, 福本敏

    Journal of Oral Biosciences　51　(Suppl.)　139-139　2009/08

  64. The KK-Periome database for transcripts of periodontal ligament development

    Saito, M, Nishida, E, Sasaki, T, Yoneda, T, Shimizu, N

    J Exp Zool B Mol Dev Evol　312B　(5)　495-502　2009/07/15

    DOI： 10.1002/jez.b.21257 　

    ISSN： 1552-5015

    More details Close

    The periodontal ligament (PDL) is a strong connective tissue that surrounds the tooth root, absorbs occlusal forces, and functions as a sense organ. PDL originated from dental follicle (DF), which possessed mesenchymal progenitors in the developing tooth germ. However, as specific marker genes for PDL and DF are currently unavailable, the molecular mechanisms of PDL development are yet to be clarified. To facilitate the identification of such genes, we have previously established a transcriptome database of the human PDL (the KK-Periome database) and screened for specific genes expressed during PDL development. Initial screening of the database revealed two marker genes for distinguishing DF and PDL. The KK-Periome database thus appears to offer a useful resource for investigating genes involved in PDL development.

  65. The KK-Periome Database for Transcripts of Periodontal Ligament Development Peer-reviewed

    Masahiro Saito, Eisaku Nishida, Takashi Sasaki, Toshiyuki Yoneda, Nobuyoshi Shimizu

    JOURNAL OF EXPERIMENTAL ZOOLOGY PART B-MOLECULAR AND DEVELOPMENTAL EVOLUTION　312B　(5)　495-502　2009/07

    DOI： 10.1002/jez.b.21257 　

    ISSN： 1552-5007

    eISSN： 1552-5015

  66. Association of tenascin-W expression with mineralization in mouse calvarial development Peer-reviewed

    Ayako Mikura, Shigeru Okuhara, Masahiro Saito, Masato Ota, Koichi Ueda, Sachiko Iseki

    Congenital Anomalies　49　(2)　77-84　2009/06

    DOI： 10.1111/j.1741-4520.2009.00227.x 　

    ISSN： 0914-3505 1741-4520

  67. 器官原基法を応用した遺伝子改変型人工歯胚作製法の開発

    和田 知子, 本間 宏実, 斉藤 正寛, 米田 俊之

    Journal of Oral Biosciences　50　(Suppl.)　112-112　2008/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

    eISSN： 1880-3865

  68. Investigating a clonal periodontal ligament progenitor/stem cell line in vitro human and in vivo Peer-reviewed

    Shinsuke Fujii, Hidefumi Maeda, Naohisa Wada, Atsushi Tomokiyo, Masahiro Saito, Akifumi Akamine

    JOURNAL OF CELLULAR PHYSIOLOGY　215　(3)　743-749　2008/06

    DOI： 10.1002/jcp.21359 　

    ISSN： 0021-9541

  69. Twist induces reversal of myotube formation Peer-reviewed

    Eleni Hjiantoniou, Mustafa Anayasa, Paschalis Nicolaou, Ioannis Bantounas, Masahiro Saito, Sachiko Iseki, James B. Uney, Leonidas A. Phylactou

    DIFFERENTIATION　76　(2)　182-192　2008/02

    DOI： 10.1111/j.1432-0436.2007.00195.x 　

    ISSN： 0301-4681

  70. Neurotrophic factor neurotrophin-4 regulates ameloblastin expression via full-length TrkB Peer-reviewed

    Keigo Yoshizaki, Shinya Yamamoto, Aya Yamada, Kenji Yuasa, Tsutomu Iwamoto, Emiko Fukumoto, Hidemitsu Harada, Masahiro Saito, Akihiko Nakasima, Kazuaki Nonaka, Yoshihiko Yamada, Satoshi Fukumoto

    JOURNAL OF BIOLOGICAL CHEMISTRY　283　(6)　3385-3391　2008/02

    DOI： 10.1074/jbc.M704913200 　

    ISSN： 0021-9258

  71. Collagen type I matrix affects molecular and cellular behavior of purified porcine dental follicle cells Peer-reviewed

    S. Tsuchiya, M. J. Honda, Y. Shinohara, M. Saito, M. Ueda

    CELL AND TISSUE RESEARCH　331　(2)　447-459　2008/02

    DOI： 10.1007/s00441-007-0532-1 　

    ISSN： 0302-766X

  72. Characteristic phenotype of immortalized periodontal cells isolated from a Marfan syndrome type I patient Peer-reviewed

    Momotoshi Shiga, Masahiro Saito, Mitsu Hattori, Chiharu Torii, Kenjiro Kosaki, Tohru Kiyono, Naoto Suda

    CELL AND TISSUE RESEARCH　331　(2)　461-472　2008/02

    DOI： 10.1007/s00441-007-0528-x 　

    ISSN： 0302-766X

  73. Increased enamel matrix genes expressions in dental epithelial cell line by co-culture with mesenchymal cell line

    Asako Matsumoto, Liming Xu, Masahiro Saito, Hidemitsu Harada, Akiyoshi Taniguchi

    8th World Biomaterials Congress 2008　4　2166　2008

  74. Characterization of human alveolar bone osteoblast

    AINO MAKOTO, SAITO MASAHIRO, MURAKAMI SHINYA, NOGUCHI TOSHIHIDE, YONEDA TOSHIYUKI

    Program and Abstracts of Annual Meeting of the Japanese Society of Periodontology　2008　71-71　2008

    Publisher: JAPANESE SOCIETY OF PERIODONTOLOGY

    DOI： 10.14833/amjsp.2008s.0.71.0 　

  75. Transcriptome database KK-Periome for periodontal ligament development: Expression profiles of the extracellular matrix genes Peer-reviewed

    Eisaku Nishida, Takashi Sasaki, Sabine Kazuko Ishikawa, Kazutaka Kosaka, Makoto Aino, Toshihide Noguchi, Toshio Teranaka, Nobuyoshi Shimizu, Masahiro Saito

    GENE　404　(1-2)　70-79　2007/12

    DOI： 10.1016/j.gene.2007.09.009 　

    ISSN： 0378-1119

  76. Association of TIMP-2 with extracellular matrix exposed to mechanical stress and its co-distribution with periostin during mouse tooth development

    N. Yoshiba, K. Yoshiba, A. Hosoya, M. Saito, T. Yokoi, T. Okiji, N. Amizuka, H. Ozawa

    European Cells and Materials　14　(SUPPL.2)　142　2007/11

    ISSN： 1473-2262

  77. Gap junctional communication regulates ameloblast differentiation

    A. Yamada, E. Fukumoto, K. Yoshizaki, K. Yuasa, S. Yamamoto, T. Iwamoto, S. Furukawa, H. Harada, M. Saito, K. Nonaka, S. Fukumoto

    European Cells and Materials　14　(SUPPL.2)　137　2007/11

    ISSN： 1473-2262

  78. Mechanisms for asporin function and regulation in articular cartilage. Peer-reviewed

    Nakajima M, Kizawa H, Saito M, Kou I, Miyazono K, Ikegawa S

    The Journal of biological chemistry　282　(44)　32185-32192　2007/11

    DOI： 10.1074/jbc.M700522200 　

    ISSN： 0021-9258

    eISSN： 1083-351X

  79. Association of TIMP-2 with extracellular matrix exposed to mechanical stress and its co-distribution with periostin during mouse mandible development Peer-reviewed

    Nagako Yoshiba, Kunihiko Yoshiba, Akihiro Hosoya, Masahiro Saito, Takamasa Yokoi, Takashi Okiji, Norio Amizuka, Hidehiro Ozawa

    CELL AND TISSUE RESEARCH　330　(1)　133-145　2007/10

    DOI： 10.1007/s00441-007-0439-x 　

    ISSN： 0302-766X

    eISSN： 1432-0878

  80. PLAP-1/asporin, a novel negative regulator of periodontal ligament mineralization Peer-reviewed

    Satoru Yamada, Miki Tomoeda, Yasuhiro Ozawa, Shinya Yoneda, Yoshimitsu Terashima, Kazuhiko Ikezawa, Shiro Ikegawa, Masahiro Saito, Satoru Toyosawa, Shinya Murakami

    JOURNAL OF BIOLOGICAL CHEMISTRY　282　(32)　23070-23080　2007/08

    DOI： 10.1074/jbc.M611181200 　

    ISSN： 0021-9258

    eISSN： 1083-351X

  81. 象牙芽細胞分化能力を有する不死化マウス歯乳頭細胞の樹立

    椿本 貴教, 高坂 一貴, 齋藤 正寛, 寺中 敏夫

    日本歯科保存学雑誌　50　(3)　292-301　2007/06

    Publisher: (NPO)日本歯科保存学会

    ISSN： 0387-2343

    eISSN： 2188-0808

  82. Wnt10a regulates dentin sialophosphoprotein mRNA expression and possibly links odontoblast differentiation and tooth morphogenesis Peer-reviewed

    Takashi Yamashiro, Li Zheng, Yuko Shitaku, Masahiro Saito, Takanori Tsubakimoto, Kenji Takada, Teruko Takano-Yamamoto, Irma Thesleff

    DIFFERENTIATION　75　(5)　452-462　2007/06

    DOI： 10.1111/j.1432-0436.2006.00150.x 　

    ISSN： 0301-4681

    eISSN： 1432-0436

  83. The development of a bioengineered organ germ method Peer-reviewed

    Kazuhisa Nakao, Ritsuko Morita, Yasumitsu Saji, Kentaro Ishida, Yusuke Tomita, Miho Ogawa, Masahiro Saito, Yasuhiro Tomooka, Takashi Tsuji

    NATURE METHODS　4　(3)　227-230　2007/03

    DOI： 10.1038/nmeth1012 　

    ISSN： 1548-7091

  84. Establishment of immortalized dental follicle cells for generating periodontal ligament in vivo Peer-reviewed

    T. Yokoi, M. Saito, T. Kiyono, S. Iseki, K. Kosaka, E. Nishida, T. Tsubakimoto, H. Harada, K. Eto, T. Noguchi, T. Teranaka

    CELL AND TISSUE RESEARCH　327　(2)　301-311　2007/02

    DOI： 10.1007/s00441-006-0257-6 　

    ISSN： 0302-766X

  85. マウス歯の発生過程におけるTIMP-2とPeriostinは類似の時間的空間的発現パターンを示す

    吉羽 永子, 吉羽 邦彦, 興地 隆史, 斎藤 正寛, 横井 隆政, 細矢 明宏, 網塚 憲生, 小澤 英浩

    Journal of Oral Biosciences　48　(Suppl.)　153-153　2006/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

    eISSN： 1880-3865

  86. Alveolar bone marrow as a cell source for regenerative medicine: Differences between alveolar and iliac bone marrow stromal cells Peer-reviewed

    Takehiro Matsubara, Ketut Suardita, Masakazu Ishii, Masaru Sugiyama, Akira Igarashi, Ryo Oda, Masahiro Nishimura, Masahiro Saito, Keigo Nakagawa, Katsuyuki Yamanaka, Kazuko Miyazaki, Masakazu Shimizu, Ujjal K. Bhawal, Koichiro Tsuji, Kozo Nakamura, Yukio Kato

    Journal of Bone and Mineral Research　20　(3)　399-409　2005/03

    DOI： 10.1359/JBMR.041117 　

    ISSN： 0884-0431

  87. Immortalization of cementoblast progenitor cells with Bmi-1 and TERT Peer-reviewed

    M Saito, K Handa, T Kiyono, S Hattori, T Yokoi, T Tsubakimoto, H Harada, T Noguchi, M Toyoda, S Sato, T Teranaka

    JOURNAL OF BONE AND MINERAL RESEARCH　20　(1)　50-57　2005/01

    DOI： 10.1359/jbmr.041006 　

    ISSN： 0884-0431

  88. Cementum matrix formation in vivo by cultured dental follicle cells Peer-reviewed

    K Handa, M Saito, M Yamauchi, T Kiyono, S Sato, T Teranaka, AS Narayanan

    BONE　31　(5)　606-611　2002/11

    DOI： 10.1016/S8756-3282(02)00868-2 　

    ISSN： 8756-3282

  89. Progenitor cells from dental follicle are able to form cementum matrix in vivo Peer-reviewed

    K Handa, M Saito, A Tsunoda, M Yamauchi, S Hattori, S Sato, M Toyoda, T Teranaka, AS Narayanan

    CONNECTIVE TISSUE RESEARCH　43　(2-3)　406-408　2002/04

    DOI： 10.1080/03008200290001023 　

    ISSN： 0300-8207

    eISSN： 1607-8438

  90. Expression of cementum-derived attachment protein in bovine tooth germ during cementogenesis Peer-reviewed

    M Saito, M Iwase, S Maslan, N Nozaki, M Yamauchi, K Handa, O Takahashi, S Sato, T Kawase, T Teranaka, AS Narayanan

    BONE　29　(3)　242-248　2001/09

    ISSN： 8756-3282

  91. Signaling reactions induced in human fibroblasts during adhesion to cementum-derived attachment protein Peer-reviewed

    M Saito, AS Narayanan

    JOURNAL OF BONE AND MINERAL RESEARCH　14　(1)　65-72　1999/01

    DOI： 10.1359/jbmr.1999.14.1.65 　

    ISSN： 0884-0431

Show all ︎Show first 5

Misc. 67

  1. 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

  2. Loss of IκBζ drives tertiary dentin formation via altering H3K4me3 status

    鈴木茂樹, YUAN Hang, 平田(土屋)志津, 根本英二, 齋藤正寛, 柴秀樹, 山田聡

    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)　155th　43-43　2021

    Publisher: (NPO)日本歯科保存学会

    DOI： 10.1177/00220345221075968 　

    ISSN： 0022-0345

    eISSN： 1544-0591

  3. 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

  4. 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

  5. Pituitary adenylate cyclase-activating polypeptide promotes eccrine gland sweat secretion

    2018/10/18

    DOI： 10.1111/bjd.14885 　

    ISSN： 0007-0963

    eISSN： 1365-2133

  6. マウスモデルを用いた根尖性歯周炎発症過程の解析

    長谷川達也, 半田慶介, 田中利典, 矢島健大, 野杁由一郎, 齋藤正寛

    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　32 (WEB ONLY)　2018/10/18

  7. 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

  8. 文献と臨床の橋わたし MSCによる再生医療の戦略とその意義(第3回) MSCによる他家移植の未来予想図

    半田 慶介, 齋藤 正寛

    日本歯科評論　78　(6)　151-154　2018/06

    Publisher: (株)ヒョーロン・パブリッシャーズ

    ISSN： 0289-0909

  9. 文献と臨床の橋わたし MSCによる再生医療の戦略とその意義(第2回) MSCによる自家移植再生療法の最前線

    半田 慶介, 齋藤 正寛

    日本歯科評論　78　(5)　155-158　2018/05

    Publisher: (株)ヒョーロン・パブリッシャーズ

    ISSN： 0289-0909

  10. ブタを用いた根管内バイオフィルムモデルの確立

    田中 利典, 半田 慶介, 兼平 正史, 長谷川 達也, 野杁 由一郎, 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　148回　26-26　2018/05

    Publisher: (NPO)日本歯科保存学会

  11. 文献と臨床の橋わたし MSCによる再生医療の戦略とその意義(第1回) MSCによる再生医療の概略

    半田 慶介, 齋藤 正寛

    日本歯科評論　78　(4)　149-152　2018/04

    Publisher: (株)ヒョーロン・パブリッシャーズ

    ISSN： 0289-0909

  12. The forefront of regenerative therapy in periodontal tissue and issues for clinical application

    Pharm stage　17　(7)　10-15　2017/10

    Publisher: 技術情報協会

    ISSN： 1346-3918

  13. ニッケルチタンファイルによる天然歯根管形成過程のX線連続撮影

    石幡 浩志, 半田 慶介, 齋藤 正寛, 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　147回　62-62　2017/10

    Publisher: (NPO)日本歯科保存学会

  14. 細胞外マトリックスを基盤とした疾患生物学 ADAMTS superfamilyを介したMarfan症候群の組織破壊機構の解析

    折本 愛, 石河 真幸, 半田 慶介, 齋藤 正寛

    Journal of Oral Biosciences Supplement　2017　181-181　2017/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

  15. Pannexin 3は新骨形成制御因子である。

    石河真幸, WILLIAMS Geneva L, 折本愛, 半田慶介, 山田吉彦, 齋藤正寛

    日本結合組織学会学術大会抄録集　49th　52　2017/06/16

  16. 結合組織破壊の分子メカニズムの新展開 ADAMTS superfamilyによるMarfan症候群の解離性大動脈瘤発症機構の解析

    折本 愛, 石河 真幸, 半田 慶介, 千々岩 みゆき, 望月 早月, 村澤 祐介, 磯貝 善蔵, 岡田 保典, 齋藤 正寛

    日本結合組織学会学術大会プログラム・抄録集　49回　54-54　2017/06

    Publisher: 日本結合組織学会

  17. ADAMTSL6βを介したMarfan症候群の解離性大動脈瘤発症機構の解析

    折本 愛, 二木 正晴, 石河 真幸, 半田 慶介, 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　146回　57-57　2017/05

    Publisher: (NPO)日本歯科保存学会

  18. Loeys-Dietz症候群モデルマウスにおけるPorphyromonas gingivalis投与による歯周組織破壊

    津島 賢一朗, 山田 聡, 木下 昌毅, 阪下 裕美, 粟田 敏仁, 山羽 聡子, 北垣 次郎太, 藤原 千春, 斎藤 正寛, 村上 伸也, 森崎 隆之

    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　146回　52-52　2017/05

    Publisher: (NPO)日本歯科保存学会

  19. 脂肪由来幹細胞を用いた歯周組織再生療法の開発 マイクロミニブタを用いた他家移植モデルの確立(Development of periodontal tissue regeneration therapy by Allogeneic transplantation of adipose derived stem cell)

    V. ベンカタ・スレッシュ, 半田 慶介, 竹立 匡秀, 村上 伸也, 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　146回　37-37　2017/05

    Publisher: (NPO)日本歯科保存学会

  20. Pannexin 3によるWnt/β-cateninおよびp21 signalingを介した骨前駆細胞の増殖機構の解析

    石河 真幸, 小林 洋子, 折本 愛, 半田 慶介, 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　145回　47-47　2016/10

    Publisher: (NPO)日本歯科保存学会

  21. 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

  22. Loeys-Dietz症候群モデルマウスを用いた歯周病の分子病態解析

    津島 賢一朗, 山田 聡, 粟田 敏仁, 山羽 聡子, 阪下 裕美, 木下 昌毅, 竹立 匡秀, 北垣 次郎太, 山下 元三, 柳田 学, 野崎 剛徳, 北村 正博, 齋藤 正寛, 村上 伸也, 森崎 隆之

    日本歯周病学会会誌　58　(秋季特別)　113-113　2016/09

    Publisher: (NPO)日本歯周病学会

    ISSN： 0385-0110

    eISSN： 1880-408X

  23. 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

  24. 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

  25. ADAMTS superfamilyによる新規結合組織破壊機構の解析

    折本 愛, 半田 慶介, 齋藤 正寛

    日本歯内療法学会学術大会プログラム・抄録集　37回　90-90　2016/06

    Publisher: 日本歯内療法学会

  26. Loeys-Dietz症候群モデルマウスを用いた歯周病の分子病態解析

    津島賢一朗, 山田聡, 粟田敏仁, 山羽聡子, 阪下裕美, 木下昌毅, 竹立匡秀, 北垣次郎太, 山下元三, 柳田学, 野崎剛徳, 北村正博, 齋藤正寛, 村上伸也

    日本歯周病学会会誌(Web)　58　2016

    ISSN： 1880-408X

  27. ADAMTSL6βを介したマルファン症候群モデルにおける組織破壊機構の解析

    折本 愛, 二木 正晴, 石河 真幸, 半田 慶介, 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　143回　40-40　2015/11

    Publisher: (NPO)日本歯科保存学会

  28. Pannexin3は細胞内ATPとCa2+濃度を調整する,骨芽細胞分化の新規制御因子である

    石河真幸, 齋藤正寛

    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　A13 (WEB ONLY)　2015/11/01

  29. S-PRGフィラー抽出液由来イオンによるマウス歯周炎モデル抑制機構の解析

    小林 洋子, 兼平 正史, 半田 慶介, 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　143回　199-199　2015/11

    Publisher: (NPO)日本歯科保存学会

  30. マルファン症候群モデルマウスにおける歯周炎の組織破壊機構に関する研究

    半田 慶介, 折本 愛, 小林 洋子, 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　142回　62-62　2015/06

    Publisher: (NPO)日本歯科保存学会

  31. ADAMTSL6βが誘導する微細線維形成によるマルファン症候群モデルマウスの大動脈瘤悪化機構の解析

    折本 愛, 半田 慶介, 村澤 裕介, 磯貝 善蔵, 齋藤 正寛

    日本結合組織学会学術大会プログラム・抄録集　47回　102-102　2015/05

    Publisher: 日本結合組織学会

  32. Loeys-Dietz症候群モデルマウスの作製と解析

    津島 賢一朗, 山田 聡, 粟田 敏仁, 山羽 聡子, 阪下 裕美, 竹立 匡秀, 北垣 次郎太, 山下 元三, 柳田 学, 野崎 剛徳, 北村 正博, 齋藤 正寛, 村上 伸也

    日本歯周病学会会誌　57　(春季特別)　111-111　2015/04

    Publisher: (NPO)日本歯周病学会

    DOI： 10.2329/perio.57.111 　

    ISSN： 0385-0110

    eISSN： 1880-408X

  33. ゲニステインによる抗炎症抑制効果のメカニズムについて

    半田 慶介, 林 敬次郎, 小池 俊之, 齋藤 正寛, 斎藤 隆史

    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　141回　134-134　2014/10

    Publisher: (NPO)日本歯科保存学会

  34. ラット口腔顔面の痛みに対するendomorphin‐1の役割

    矢島健大, 佐藤匡, 市川博之, 齋藤正寛

    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)　139th　P56 (WEB ONLY)　2013/10/01

  35. サイエンス 次世代の歯科治療システムとしての歯科再生治療--組織修復再生治療と臓器置換再生治療としての歯の再生

    大島 正充, 齋藤 正寛, 辻 孝

    日本歯科医師会雑誌　64　(5)　511-522　2011/08

    Publisher: 日本歯科医師会

    ISSN： 0047-1763

  36. 歯科再生医療はどこまで到達し、どこへ向かうのか? 歯根再生のキーワードとしての「HERS」のメカニズムに迫る

    大島 勇人, 藤原 尚樹, Jung Han-Sung, 太田 正人, 齋藤 正寛, 原田 英光

    歯界展望　111　(5)　953-962　2008/05

    Publisher: 医歯薬出版(株)

    ISSN： 0011-8702

  37. Comprehensive analysis of tissue-specific markers involved in periodontal ligament development

    Masahiro Saito, Eisaku Nishida, Toshiyuki Yoneda

    Journal of Oral Biosciences　50　(3)　175-182　2008

    Publisher: Japanese Association for Oral Biology

    DOI： 10.2330/joralbiosci.50.175 　

    ISSN： 1349-0079

  38. Neurotrophic factor NT-4 regulates ameloblastin expression

    K. Yoshizaki, A. Yamada, K. Yuasa, S. Yamamoto, T. Iwamoto, H. Harada, M. Saito, E. Fukumoto, K. Nonaka, S. Fukumoto

    European Cells and Materials　14　(SUPPL.2)　143　2007/11/01

    ISSN： 1473-2262

  39. Wnt10a regulates dentin sialophosphoprotein mRNA expression and possibly links odontoblast differentiation and tooth morphogenesis

    Takashi Yamashiro, Li Zheng, Yuko Shintaku, Masahiro Saito, Takanori Tsubakimoto, Kenji Takada, Teruko Takano-Yamamoto, Irma Thesleff

    European Cells and Materials　14　140　2007/11/01

    ISSN： 1473-2262

  40. ADAMTSL-4はFibrillin-1と協調してオキシタラン線維形成に関わる

    高坂 一貴, 齋藤 正寛, 大島 勇人, 須田 直人, Ganburged Ganjargal, 寺中 敏夫, 米田 俊之

    Journal of Oral Biosciences　49　(Suppl.)　205-205　2007/08

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

  41. ADAMTSL-4とFibrillin-1はオキシタラン線維形成を介して歯根膜発生に協調的に働く

    高坂 一貴, 齋藤 正寛, 筒井 仰, 眞鍋 理一郎, 清野 透, 大島 勇人, 須田 直人, Ganjargal Ganburged, 関口 清俊, 米田 俊之

    日本結合組織学会学術大会・マトリックス研究会大会合同学術集会プログラム・抄録集　39回・54回　121-121　2007/05

    Publisher: 日本結合組織学会・マトリックス研究会

  42. The development and in vivo transplantation of an artificial tooth germ reconstituted by the bioengineered organ germ method.

    Kazuhisa Nakao, Ritsuko Morita, Yasumitsu Saji, Kentaro Ishida, Miho Ogawa, Masahiro Saito, Yasuhiro Tomooka, Takashi Tsuji

    European Cells and Materials　14　59　2007

  43. Expression of TIMP-2 and Periostin during Mouse Tooth Development

    YOSHIBA Nagako, YOSHIBA Kunihiko, OKIJI Takashi, SAITO Masahiro, YOKOI Takamasa, HOSOYA Akihiro, OZAWA Hidehiro

    49　98-98　2006/04/21

    ISSN： 0387-2343

  44. 不死化マウス歯小嚢細胞における腱表現型の解析

    横井 隆政, 斎藤 正寛, 椿本 貴教, 西田 英作, 原田 英光, 野口 俊英, 寺中 敏夫

    Journal of oral biosciences　46　(5)　454-454　2004/09/01

    Publisher: 歯科基礎医学会

    ISSN： 1349-0079

  45. 歯周病の病態と新たな治療 セメント質マーカー分子に基づいたセメント質形成機構の解析

    齋藤 正寛, 半田 慶介, 清野 透, 寺中 敏夫

    炎症・再生　24　(4)　398-398　2004/07

    Publisher: 日本炎症・再生医学会

    ISSN： 1346-8022

  46. Cementum matrix formation by cultured dental follicle cells in vivo.

    K Handa, M Saito, M Yamauchi, T Kiyono, S Sato, T Teranaka

    JOURNAL OF DENTAL RESEARCH　82　403-403　2003/12

    ISSN： 0022-0345

  47. エナメル質形成不全症の患者より単離した培養歯根膜細胞の解析

    北原 裕, 須田 直人, 斉藤 正寛, 大山 紀美栄

    歯科基礎医学会雑誌　45　(5)　369-369　2003/09/01

    Publisher: 歯科基礎医学会

    ISSN： 0385-0137

  48. Cementum matrix formation by cultured dental follicle cells in vivo.

    K. Handa, M. Saito, M. Yamauchi, T. Kiyono, S. Sato

    JOURNAL OF DENTAL RESEARCH　82　B325-B325　2003/06

    ISSN： 0022-0345

  49. 歯小嚢細胞を用いたセメント質形成機構の解析

    半田 慶介, 服部 慎太郎, 斎藤 正寛, 山内 雅人, 豊田 實, 佐藤 貞雄, 寺中 敏夫

    マトリックス研究会大会　(50)　66-66　2003/03

    Publisher: マトリックス研究会

    DOI： 10.14919/matrixclubmeeting.50.0.54.0 　

  50. 歯小嚢細胞を用いたセメント質形成機構の解析

    半田 慶介, 服部 慎太郎, 斎藤 正寛, 山内 雅人, 豊田 實, 佐藤 貞雄, 寺中 敏夫

    マトリックス研究会大会　(50)　66-66　2003/03

    Publisher: マトリックス研究会

    DOI： 10.14919/matrixclubmeeting.50.0.54.0 　

  51. ウシ歯胚におけるセメント質過形成モデルの解析

    半田 慶介, 角田 晃, 山内 雅人, 服部 慎太郎, 斉藤 正寛, 豊田 實, 佐藤 貞雄, 寺中 敏夫

    神奈川歯学　37　(抄録集)　22-22　2002/12

    Publisher: 神奈川歯科大学学会

    ISSN： 0454-8302

  52. 歯周組織再生医療へのアプローチ ウシ歯胚より採取した歯小嚢細胞のセメント質形成能について

    齋藤 正寛, 半田 慶介, 木下 靱彦, 寺中 敏夫

    日本口腔科学会雑誌　51　(6)　485-485　2002/11

    Publisher: (NPO)日本口腔科学会

    ISSN： 0029-0297

  53. Cementum Matrix Formation by Cultured Bovine Dental Follicle cells

    Saito Masahiro, Handa Keisuke, Teranaka Toshio

    Journal of the Japanese Association of Periodontology　44　130-130　2002/09/30

    Publisher: The Japanese Society of Periodontology

    ISSN： 0385-0110

  54. セメント質過形成モデルの解析

    半田 慶介, 角田 晃, 服部 慎太郎, 齋藤 正寛, 豊田 實, 寺中 敏夫

    歯科基礎医学会雑誌　44　(5)　427-427　2002/09/20

    Publisher: 歯科基礎医学会

    ISSN： 0385-0137

  55. 歯の再生 (再生医学・再生医療) -- (第4部 組織再生・臓器再生の展望)

    原田 英光, 斎藤 正寛

    現代化学増刊　(41)　175-177　2002/07

    Publisher: 東京化学同人

    ISSN： 0910-4747

  56. 移植ウシ歯小嚢組織より形成されたセメント芽細胞腫様構造物の解析

    半田 慶介, 角田 晃, 斉藤 正寛, 寺中 敏夫

    日本歯科保存学雑誌　45　(春季特別)　115-115　2002/04

    Publisher: (NPO)日本歯科保存学会

    ISSN： 0387-2343

  57. バキュロウィルス-昆虫細胞発現系によるヒト骨シアロタンパク質の作製

    角田 晃, 齋藤 正寛, 半田 慶介, 寺中 敏夫, 山内 雅人, 堀口 美和, 佐藤 貞雄

    神奈川歯学　36　(抄録集)　50-50　2001/12

    Publisher: 神奈川歯科大学学会

    ISSN： 0454-8302

  58. バキュロウィルス発現系を用いたヒトオステオポンチンの発現及びその精製

    堀口 美和, 山内 雅人, 佐藤 貞雄, 斎藤 正寛, 半田 慶介, 角田 晃, 寺中 敏夫

    神奈川歯学　36　(抄録集)　27-27　2001/12

    Publisher: 神奈川歯科大学学会

    ISSN： 0454-8302

  59. 培養歯小嚢細胞のin vivoでのセメント質マトリックス形成について

    半田 慶介, 齋藤 正寛, 寺中 敏夫, 山内 雅人, 佐藤 貞雄

    神奈川歯学　36　(抄録集)　51-51　2001/12

    Publisher: 神奈川歯科大学学会

    ISSN： 0454-8302

  60. 組み換えバキュロウィルスを用いたヒト骨シアロタンパク質の作製

    角田 晃, 齋藤 正寛, 半田 慶介, 寺中 敏夫

    日本歯科保存学雑誌　44　(秋季特別)　139-139　2001/10

    Publisher: (NPO)日本歯科保存学会

    ISSN： 0387-2343

  61. ウシ歯小嚢由来細胞中に存在する前駆体細胞のセメント芽細胞への分化誘導について

    半田 慶介, 齋藤 正寛, 角田 晃, 寺中 敏夫, 山内 雅人, 佐藤 貞雄, 服部 慎太郎, 豊田 實, 槻木 恵一, 渡邊 是久

    神奈川歯学　35　(抄録集)　15-15　2000/12

    Publisher: 神奈川歯科大学学会

    ISSN： 0454-8302

  62. ウシ歯小嚢由来細胞中に存在する前駆体細胞のin vivoにおけるセメント芽細胞への分化誘導について

    半田 慶介, 齋藤 正寛, 角田 晃, 寺中 敏夫

    日本歯科保存学雑誌　43　(秋季特別)　48-48　2000/10

    Publisher: (NPO)日本歯科保存学会

    ISSN： 0387-2343

  63. Expression of cementum matrix proteins in bovine dental follicle cells.

    M Saito, K Handa, A Tsunoda, S Hattori, M Toyoda, M Yamauchi, K Sasaguri, S Sato, T Teranaka

    JOURNAL OF BONE AND MINERAL RESEARCH　15　S346-S346　2000/09

    ISSN： 0884-0431

  64. ウシ歯胚由来歯小嚢細胞の培養系の確立

    半田 慶介, 角田 晃, 齋藤 正寛, 寺中 敏夫, 山内 雅人, 笹栗 健一, 佐藤 貞雄

    歯科基礎医学会雑誌　42　(5)　462-462　2000/08/30

    Publisher: 歯科基礎医学会

    ISSN： 0385-0137

  65. ウシ歯胚由来歯小嚢細胞培養系の確立

    半田 慶介, 角田 晃, 齋藤 正寛, 寺中 敏夫

    日本歯科保存学雑誌　43　(春季特別)　142-142　2000/03

    Publisher: (NPO)日本歯科保存学会

    ISSN： 0387-2343

  66. Expression of cementum matrix proteins in bovine dental follicle cells.

    K Handa, A Tsunoda, M Saito, K Sasaguri, M Yamauchi, S Sato, T Teranaka

    JOURNAL OF DENTAL RESEARCH　79　472-472　2000

    ISSN： 0022-0345

  67. ウシ歯小嚢細胞から採取されたセメント芽細胞前駆体の培養系の確立

    半田 慶介, 角田 晃, 斎藤 正寛, 寺中 敏夫, 山内 雅人, 笹栗 健一, 佐藤 貞雄

    神奈川歯学　34　(抄録集)　41-41　1999/12

    Publisher: 神奈川歯科大学学会

    ISSN： 0454-8302

Show all ︎Show first 5

Research Projects 49

  1. Development of a novel bone regeneration technique using endochondral ossification by skeletal stem cells.

    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

    2024/04/01 - 2027/03/31

  2. 歯周組織特異的CAR-MSC細胞を用いた革新的な歯周組織再生移植治療への挑戦

    山田 聡, 向阪 幸彦, 齋藤 正寛, 梶川 哲宏, 鈴木 茂樹

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 挑戦的研究(萌芽)

    Institution: 東北大学

    2023/06/30 - 2025/03/31

  3. 炎症性腸疾患の疾患活動度をモニターする唾液マーカーの探索

    兼平 正史, 八幡 祥生, 齋藤 正寛, 角田 洋一

    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

    2022/04/01 - 2025/03/31

  4. 治療抵抗性口腔疾患に対する革新的抗炎症療法の確立

    齋藤 正寛, 八幡 祥生, 田中 志典, 祖山 均

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 挑戦的研究(萌芽)

    Institution: 東北大学

    2021/07/09 - 2024/03/31

    More details Close

    近年口腔と全身疾患に関して多くの因果関係が明らかにされており、循環器疾患、自己免疫疾患、内分泌疾患などの全身疾患により産生が亢進される炎症性サイトカインやリンパ循環を介した炎症性細胞の循環が口腔内炎症の遷延に寄与していると指摘されている。特にヒト最大の免疫組織である腸管免疫の破綻により発症する炎症性腸疾患（IBD)は、腸のみならず全身の免疫機構の低下を招き、口腔内でも根尖性歯周炎、歯周炎等の口腔内炎症性疾患のハイリスクになることが知られており口腔と全身疾患を繋ぐ臓器炎症ネットワークに注目が集まっている。 本年度は既に当研究室で確立した炎症腸疾患に根尖性歯周炎（AP)を発症させるIBD-APモデルを用いて、腸炎による顎骨破壊増悪化機構の解析を実施した。IBDによる体重減少、腸粘膜上皮の破壊、腸管の狭小及び短縮化が観察された。IBD-APを観察すると、AP単独と比較して顎骨内で形成される病変が拡大することが観察された。この結果よりIBDは顎骨における炎症性破壊を増悪化する可能性が示されたため、RNA-seq解析で分析を行った。その結果、IBDを発症することで顎骨内で既に炎症反応が起きており、IBD-APになると白血球の活性化、リンパ球浸潤に伴う炎症マーカーの発現上昇が確認された。組織解析を行うと、IBDを発症した顎骨内で既に根尖部の歯周組織の破壊が観察され、さらにIBD-APになると病変内に壊死細胞を中心にその周囲に炎症系細胞の浸潤を伴う病変が根尖部顎骨内に形成されていた。根管内のドラッグデリバリーシステムの開発を行うため、ラットAPモデルに着手し、顎骨破壊を伴う根尖部病変の形成を確認した。

  5. Mechanism of undifferentiated maintenance immature osteoblasts under microgravity environment

    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: Kanagawa Dental College

    2021/04/01 - 2024/03/31

  6. 類骨オルガノイドを用いた革新的造骨再生医療実用化のための研究基盤構築

    齋藤 正寛, 稲垣 雅彦, 八幡 祥生, 山田 聡, 田中 志典

    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

    2021/04/01 - 2024/03/31

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    研究代表者はヒト顎骨から独自の酵素消化法にて骨再生医療に特化したヒト未分化骨芽細胞様細胞（Human Alveolar bone derived OsteoBlast:HAOB)の分離培養技術を世界に先駆けて確立してきた。HAOBはあらゆる年代の患者層から採取することが可能な造骨細胞であり、分化誘導することなく移植後に骨形成を誘導することが出来る。一方、産総研と共同で体内にて分解・代謝されるポリ乳酸を主成分とし、HAOBの増殖と骨芽細胞分化に最適となるよう硬さ等を調製した生体吸収性移植材料（綿状PLLA）を開発し、特許を取得している。（特許6901727：歯槽骨由来の未分化骨芽細胞と歯槽骨由来の未分化骨芽細胞用担体との複合物及びその利用、登録日：2021.07.06） これまでの研究で、HAOBは免疫反応のため異種移植では骨形成を誘導出来ないことが判明している。これらの結果から今年度は、マウスを用いてヒト水平性骨欠損を模倣した動物モデルを作成し、in vivoにおいて骨形成能の検証ができる系を確立してきた。この系を用いて、マウス頭蓋冠よりHAOBと同じ手法で得た未分化骨芽細胞（MCOB）を分離培養し、綿状PLLAに細胞を混入させた移植材料（MCOB-綿状PLLA）を顎骨欠損部位へ移植し、骨再生能を検証した。その結果、適応承認品である炭酸アパタイト製品のCytransあるいは綿状PLLA単独移植群と比較してMCOB-綿状PLLAは顎骨欠損部位で良好な骨造成が確認され、MCOBを使用する優位性を証明出来た。これらの研究成果を踏まえて、次年度はマウスモデルにおける再生骨の機能解析、およびHAOBの臨床可能な培地を用いた分離培養技術の開発を目指す。

  7. 炎症性腸疾患併発下で難治化する根尖性歯周炎の分子病態解析と新規治療標的の検索

    八幡 祥生, 齋藤 正寛, 山田 聡, 半田 慶介, 野杁 由一郎

    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

    2020/04/01 - 2023/03/31

    More details Close

    本研究は、全身疾患下で増悪化ならびに治療抵抗性化する根尖性歯周炎の病態機構を解明し、アンメット・メディカル・ニーズとなっている治療抵抗性根尖性歯周炎に対する新規治療基軸を構築することを目的としている。その中で我々は、全身疾患の1つ、炎症性腸疾患（IBD）に着目した。IBDによる腸管免疫の破綻は、腸の炎症のみならず全身各所の炎症を増悪させる難治疾患であり、臨床報告において根尖性歯周炎との関連が指摘されている。これまでにIBDモデルマウスを用いて根尖性歯周炎を併発させることで、根尖性歯周炎が増悪化することを見出してきた。昨年度は、その炎症動態の分子免疫機構を解明するために、網羅的遺伝子解析およびフローサイトトメトリーによる解析を進めた。その結果、IBDを併発することにより、通常の根尖性歯周炎よりも、明らかに炎症関連遺伝子の発現が上昇すること、その炎症増悪には好中球、単球／マクロファージ、Th17が特に関連していることを明らかにした。発現遺伝子群については炎症関連遺伝子、特に好中球の脱顆粒に関連した遺伝子が多く発現していることを見出した。さらに、IBD単独発症群においても顎骨内に炎症関連遺伝子発現の亢進を確認した。この事実は、ヒトで確認されているIBDが契機となって生じる全身各所の炎症の増悪化と矛盾しない。つまり、IBDによりすでに全身的に炎症が亢進しているところに、根尖性歯周炎などのPAMPs/DAMPsなどのデンジャーシグナルが加わることによって、その炎症が難治化するという病態機構が考えられる。次年度は、この増悪化する炎症にさらに着目し、治療標的群の検討および介入効果の検討を図る予定である。

  8. 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

    2020/07/30 - 2022/03/31

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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.

  9. Development of the new regenerative medicine technique by applying the mechanism of the cytoskeleton reorganization.

    Nishida Eisaku

    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: Aichi Gakuin University

    2017/04/01 - 2022/03/31

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    There are various regenerative therapies for periodontal disease, which is highly prevalent in middle-aged and elderly people. There is a need for cell transplantation therapy in the periodontal disease category, but the method is currently poorly established. The function of NEBL as a bone marker molecular candidate for alveolar bone-derived osteoblasts that can be used for cell transplantation therapy in this study in the bone differentiation cascade needs to be further investigated in mice and rats. . In addition, it was clarified that the establishment of a method for culturing osteoblasts derived from alveolar bone of old rat alveolar bone is useful as a model animal in diseases associated with bone defects such as periodontal disease assuming middle-aged and elderly people.

  10. Development of new 3D bone regenerative medicine technology for horizontal bone defects using human ES cells

    Handa Keisuke

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

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

    2018/04/01 - 2021/03/31

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    The ultimate goal of this research application is to generate osteoblasts by inducing differentiation of human ES cell-derived mesenchymal stem cells, and finally to create an artificial bone matrix for use as a bone filling material. Therefore, in vitro differentiation induction experiments were conducted using mouse osteoblast-derived cell lines to improve differentiation conditions. In addition, for the differentiation induction experiment by transplantation experiment to immunodeficient mouse for artificial bone matrix preparation, mouse osteoblast-derived cell line was transplanted subcutaneously to the back of immunodeficient mouse, and the final artificial bone matrix was prepared. I specified the size.

  11. Clarification of novel tissue destruction mechanism induced by mechanobiology breakdown

    Saito Masahiro

    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

    2018/04/01 - 2021/03/31

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    In order to investigate the effect of mechanical force on the development of connective tissue disease, we generated ADAMTSL6-deficient mice, which are polymerization regulators of elastic fibers that play a critical for regulating tissue strength. ADAMTSL6 is an extracellular matrix that promotes the polymerization of fibrillin-1microfibril, which is essential to elastic fiber formation. ADAMTSL6 has two types, alpha and beta, and that alpha knockout mice is embryonic lethality and beta knockout mice able to survive. An apical periodontitis model was performed to investigate if ADAMTSL6 beta knockout mice the effects of connective tissue disease. Result indicated that ADAMTSL6 beta knockout mice clearly induced bone destruction in this model. From these result, reduction of elastic fibers strength may cause connective tissue disease.

  12. Molecular mechanisms of p75NTR modulation in the regeneration of pulp sensory function

    Inuzuka Hiroyuki

    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

    2018/06/29 - 2020/03/31

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    Efficient regeneration of pulp sensory function requires neural and axon regeneration and proper axon guidance in the dental pulp. In this study, we focused on the regulatory mechanisms of p75 neurotrophin receptor (p75NTR), an essential factor for neural differentiation, survival, and axon elongation. We found that post-translational modifications play a role in the regulation of p75NTR and modulate its activity. The findings of this study will provide an insight into developing a potential approach for the efficient regeneration of pulp function.

  13. Development of high predictive bone regeneration method applying quantitative control mechanism of osteoblast differentiation factor

    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

    2017/04/01 - 2020/03/31

  14. Modulation of lipid homeostasis in maintenance and directed differentiation of mesenchymal stem cells

    Inuzuka 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

    2016/04/01 - 2019/03/31

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    Manipulating lipid biosynthesis in stem cells could be a potential approach for highly efficient directed differentiation of mesenchymal stem cells. In this study, we identified the molecular mechanisms of the proteasome-dependent degradation of Lipin1 that plays critical roles in lipid homeostasis. Our finding will provide insights into the development of novel strategies for the directed differentiation of mesenchymal stem cells through Lipin1 protein stability control.

  15. The development of anti-inflammatory and regenerative medicine for periodontitis: application of Pannexin 3 signaling pathways.

    Masaki Ishikawa, YAMADA yoshihiko

    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

    2016/04/01 - 2019/03/31

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    Coping with the hyper-aging society, an advanced treatment for periodontal disease is necessary in order to maintain the quality of life. Here, we show that Pannexin 3 (Panx3), a member of gap junction protein is a new regulator to switch from proliferation to differentiation of chondroprogenitors and osteoprogenitors via multiple Panx3 signaling pathways. We demonstrated that Panx3 has potentials for new medical treatment and drug application in periodontitis by promoting bone regeneration.

  16. Development of novel diagnostic technology for marfan syndrome using periodontal tissue

    Saito Masahiro

    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

    2016/04/01 - 2018/03/31

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    Marfan syndrome is a genetic connective tissue disease that caused by mutation of fibrillin-1 that is a major component of microfibril. Main cause of death of marfan syndrome is aortic aneurysm and dissection, however no reliable diagnostic method is available at present. In this project, we tried to develop a novel diagnostic technology of aortic aneurysm and dissection that investigating microfibril structure using anti-fibrillin-1 antibody. We generated immunostaining technology that is able to stain microfibril in the human aorta using anti-fibrillin-1 antibody. The diagnostic technology that suspect aortic aneurysm and dissection is going to develop by using gigival tissue obtained from marfan syndrome patient.

  17. Development of a method for the endochondral alveolar bone tissue engineering using iPS cells

    Egusa Hiroshi, SAITO Masahiro, FUKUMOTO Satoshi, OKAWA Hiroko, KOSAKA Yukihiro

    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

    2016/04/01 - 2018/03/31

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    A strategy of induced pluripotent stem (iPS) cell-based alveolar bone regeneration is expected to improve treatment outcome in prosthetic treatments. We focused on possible advantage in endochondral bone regeneration in the large bone defect. The aim of this study was to develop a method to fabricate bone/cartilage-like cell constructs using iPS cells. We found that combination use of chondrogenic and osteogenic induction factors could guide mouse iPS cell embryoid bodies into hybrid bone/cartilage-like cell constructs on the manipulation of a ratio in degrees of chondrocyte/osteoblast differentiation.

  18. Creation of next generation cell therapy for periodontal tissue based on allogenic cell transplantation

    HANDA Keisuke, DEZAWA Mari

    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

    2015/04/01 - 2018/03/31

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    We decided to aim for the development of regenerative medicine technology by transplantation using an adipose tissue-derived multilineage progenitor cells (ADMPC). Comparison of regeneration effect of alveolar bone by autologous transplantation of ADMPC and microinhibition periodontitis model with root bifurcation second grade lesion was carried out. As a result of analyzing alveolar bone regeneration ability with uCT in three dimensional images, it was confirmed that the transplantation of pADMPC with osteogenesis had alveolar bone regeneration effect comparable to autologous transplantation. Based on the results of this study, the immunomodulatory capacity possessed by ADMPC was expected to be effective in restoring the function of periodontal tissues in other transplantation.

  19. The development of a novel preventive method of periodontal disease using S-PRG Filler eluate

    Iwamatsu-Kobayashi Yoko, SUZUKI OSAMU

    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

    2014/04/01 - 2017/03/31

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    S-PRG filler, a component of composite resin, is capable of releasing 6 metal ions that possess antibacterial activity against caries and periodontal pathogens. Although S-PRG has been suggested to be involved in oral disease prevention, no reports have been published regarding its preventive effect on periodontal disease in vivo. The present study investigated whether the eluate from S-PRG (S-PRG eluate) has a preventive effect on a mouse model of ligature-induced periodontal disease. C57BL/6 mice were divided into three groups; no ligature, ligature and ligature with S-PRG eluate group. S-PRG eluate clearly inhibited alveolar bone loss of ligature-induced periodontal disease and reduced the infiltration of inflammatory cells. TOF-SIMS analysis revealed that more boron ions were present in the S-PRG group. Our results suggest that the S-PRG eluate has a preventive effect against tissue destruction in periodontal disease through its anti-inflammatory effects in vivo.

  20. Regulation and analysis of tooth and salivary gland morphogenesis

    FUKUMOTO EMIKO

    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

    2014/04/01 - 2017/03/31

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    To regenerate of tooth and salivary gland, it is important to identify the gene associated with the regulation of morphogenesis. However, it has never clearly understood the morphogenesis of tooth and salivary gland. Here, we identified the genes specifically expressed in tooth germ using microarray gene screening. Mst1 is one of the Hippo pathway molecule expressed in embryonic tooth germ. Over expression of Mst1 in dental epithelial cells showed inhibition of proliferation. On the other hand, suppression of Mst1 expression using siRNA showed enhanced proliferation. Further, knockdown of Mob1 in mice, which is down stream molecule of Mst1, showed enhanced tooth size. Moreover, we identified the regulation of tooth width by NF-kB singaling molecule, NIK and p50. Further, GDF5 down-regulated enamel formation. These information is useful for establish the regeneration of tooth and salivary gland.

  21. Development of novel therapeutics for the treatment of marfan syndrome using iPS technology

    Saito Masahiro

    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

    2014/04/01 - 2017/03/31

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    Marfan syndrome (MFS) that is a severe, systemic disorder of connective tissue with predominant involvement of the ocular, cardiovascular and musculoskeltal system. Cardiovascular manifestations in the form of dissecting thoracic aortic aneurysms, mitral valve prolapse and myocardial dysfunction are the major cause of morbidity and mortality in MFS. The molecular pathogenesis of MFS proceeded principally through the activation of TGF-beta signaling and metalloproteinase expression have shown to cause as a common mechanisms that leads to aortic degeneration. Here we showed the novel mechanisms of ADAMTSL6beta on the accelerating ADAMTS4 activity to progress aortic aneurysm and dissection in MFS through versican degradation. Thus, our results suggest that recruitment of ADAMTS4 to fibrillin-1 microfibril by ADAMTSL6beta promotes versican degradation and that this axis may provide a new insight for pathogenesis of aortic aneurysm and dissection in MFS.

  22. Regulation and determination of organ derived from invaginated epithelium

    FUKUMOTO SATOSHI

    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: Tohoku University

    2014/04/01 - 2017/03/31

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    Tooth and hair are formed by invagination of epithelium. Invaginated epithelium interacts with neural crest derived mesenchymal tissues, and then formed tooth and hair. However, mechanism of organ determination has never clearly understood. Sox21 is one of the transcription factor, and expressed in dental epithelium. Sox21 knockout mice showed hair formation in incisor indicating that Sox21 may be involved in the determination of organs. Decrease Sox21 inhibited ameloblast marker gene expression, and induced hair marker genes including keratins. ChipSeq analysis showed that Sox21 directly binds to Anapc10 gene promoter region and regulated their expression in dental epithelium. In Sox21 knockout mice, Anapc10 expression was decreased in tooth germ. Further, Sox21 over expression induced Anapc10 expression. These results suggested that Sox21 regulates Anapc10 expression and organ determination.

  23. Efficacy and mechanism of Multilineage-differenciating Stress Enduring Cell transplantation in experimental abdominal aortic aneurysm

    TAKAHASHI GORO, Katsuhiro Hosoyama

    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

    2014/04/01 - 2017/03/31

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    Cell therapies for aortic aneurysms (AAs) have advantages of non-invasiveness compared to surgical therapies. However previously reported cell therapies had only limited therapeutic effect. With the aim of evaluation the efficacy of multi-lineage differentiating stress enduring cells (Muse cells), which are a kind of pluripotent stem cells with unique features, abdominal aortic aneurysms were induced in mice models and assessed the AAs diameter after cell transplantation. Muse cells were collected from human bone marrow mesenchymal stem cells by FACS sorting with SSEA-3 staining. The mean diameters of AAs in Muse group were significantly smaller than other groups. The immunofluorescent assessment demonstrated that some smooth muscle cells and endothelial cells were derived from injected Muse cells. These data suggest that Muse cells can fix AAs by regenerating the damaged cell components of aortic wall.

  24. Development of novel anti-inflammatory therapy for apical periodontal disease using mesenchymal cell transplantation

    Masahiro Saito, YOSHIDA KYOKO, KOBAYASHI YOKO, SAITO TADAO

    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

    2014/04/01 - 2016/03/31

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    In the present study, we attempt to develop anti-inflammatory therapy for apical periodontitis. To achieve this purposes, we investigate matricellular proteins which is a extracellular matrix involving acceleration of immune response. We found that reduced expression of fibrillin-1 that regulate tissue elasticity is excavated inflammatory response of periodontal tissue. From these findings, reduction of fibrillin-1 play an important role in the progression of apical periodontal disease. We also established alveolar bone derived immature osteoblast obtained from human alveolar bone. These cells has a high osteogenic ability and bone forming ability in vivo. We are investigating anti-inflammatory effect of these cells.

  25. Function and regulation of gap junction on oral epithelium organogenesis

    Yamada Aya, NAKAMURA TAKASHI, SAITO MASAHIRO, SAKAI TAKAYOSHI, IWAMOTO TSUTOMU

    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

    2012/04/01 - 2016/03/31

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    Connexin 43 is one of the gap junction protein. To understand the role of connexin 43 (Cx43) in salivary gland development, first we examined the expression of Cx43 by immunostaining using their specific antibody. Cx43 expressed terminal bud epithelum of salivary gland, but not in mesenchymal tisuue. In Cx43 knockout mice, branching morphogenesis of submandibular gland was dramatically inhibited. In presence of inhibitory peptide for Cx43 function, branching morphogenesis of salivary gland organ culture was also inhibited as similar to Cx43 knockout mice. From our results, Cx43 is necessary for salivary gland development and terminal bud branching. Further, gap junctional communication is important for the determination of cell fate. These information is useful for understanding the molecular mechanism of salivary gland development and regeneration.

  26. Elucidate the regulational mechanism of tooth bud formation

    NAKAMURA TAKASHI, SAKAI Takayoshi, SAITO Masahiro, FUKUMOTO Satoshi

    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

    2012/04/01 - 2015/03/31

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    The final goal of this study is to elucidate the molecular mechanism of the regulation in the number of teeth by novel transcription factor Epiprofin in tooth germ formation and development. Our analysis of Epfn KO mice revealed that Epiprofin promotes the transitory cell proliferative activities in keratinocyte as well as dental epithelial cells. In Epfn KO mice, keratinocytes and dental epithelial cells keep migrating into dental mesenchyme due to the decrease of proliferation activity and apoptosis of cells. In addition, Epfn contributes to activate the cell proliferation of Transit Amplifying cells produced from stem cells through Notch signaling. Furthermore Epfn exerts a critical role in cell fate determination of dental epithelial cells and epithelial stem cells.

  27. Molecular analysis of inflammasome in periodontal tissue destruction and regeneration.

    YAMADA SATORU, MURAKAMI Shinya, KITAMURA Masahiro, YANAGITA Manabu, SAITO Masahiro, YAMAMOTO Teruko, MORISAKI Takayuki

    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: Osaka University

    2011/04/01 - 2014/03/31

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    In this study, we investigated expression pattern of inflammasome in periodontal tissue and cells to assess the involvement of inflammasome in periodontal tissue homeostasis, destruction and regeneration. It was shown that inflammasome-associated molecules are expressed in periodontal tissues and cells in normal conditions and these expressions are up-regulated in inflammatory conditions. Periodontal ligament associated extracellular matrix (PDL-ECM) proteins show the interaction with inflammasome, suggesting the regulation of tissue-homeostasis and inflammatory responses by PDL-ECM-inflammasome pathway.

  28. Molecular mechanisms of BSP gene transcription on cementblast

    YAMAUCHI Masato, SAITO Masahiro

    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: Kanagawa Dental College

    2011 - 2013

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    Bone Sialoprotein(BSP) is a tissue-specific marker of cementblast cells which has shown to be transformed from Hertwig's epithlial cells.To elucidate the mechanisms of gene transcription,3 putative osteoblast specific element 2 consensus motif(OSE2-1~OSE2-3) were investigated the ability of Runx2 to interact with cognate cis-acting elements. Forced expression of Runx2 induced 14 fold enhancement of transcription activity observed with the 6 x tandem repeats of OSE2-2 and 3 fold enhancement with that of OSE2-3, whereas 60% significant reduction was observed with that of OSE2-1. Chromatin immunorecipitation analyses revealed Runx2 were significantly higher recruited to OSE2-2 than to other OSE2s in vivo. BMP-2 increased Runx2 binding to these OSE2s and its transcription, whereas obvious reduction of OSE2-2 transcription induced by TGF-beta 1. These data suggested that the coordinated regulation of chromatin on respective OSE2s with Runx2 were modulated by TGF-beta/BMP signals.

  29. Establishment of screening system for novel therapeutics for periodontal disease by using low molecule compound

    SAITO Masahiro, TSUJI Takashi, YAMADA Satoru

    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: Tokyo University of Science

    2011 - 2012

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    We have shown that regeneration of periodontal tissue is required for reorganization of microfibril. To develop a novel therapeutics for periodontal disease, we attempt to develop low molecular compoundto stimulate expression of ADAMTSL6・in which promotion of microfibril assembly. To achieve these purposes, we demonstrated that generation of cell possessing EGFP reporter under control by ADAMTSL6・promoter.

  30. Analysis of regeneration ability of periodontal ligament by ADAMTSL4 and development of novel therapeutic for conservative dentistry

    SAITO Masahiro, TERANAKA Toshio, TSUJI Takashi

    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: Tokyo University of Science

    2009 - 2011

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    Marfan's syndrome(MFS) is a systemic disorder of the connective tissues including periodontal ligament(PDL) by insufficiency of fibrillin-1 microfibril formation and can cause severe periodontal disease. ADAMTSL6β, a microfibril-associated extracellular matrix protein that has been implicated in fibrillin-1 microfibril assembly is able to improve microfibril insufficiency of PDL in MFS mice model. These findings suggest ADAMTSL6β-mediated fibrillin-1 microfibril assembly develop as a new therapeutic of conservative dentistry for the treatment of periodontal disease in MFS.

  31. 遺伝子改変マウス作製技術を応用した歯根膜再生モデル動物の開発

    齋藤 正寛, 山田 聡

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 挑戦的萌芽研究

    Institution: 東京理科大学

    2009 - 2010

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    歯根膜は歯を支える靭帯構造を有する結合組織で、機械的外力に耐える構造を有する。この組織は歯周病の標的組織でありことから、歯周病の効果的な治療薬を開発するためには、歯根膜再生の分子メカニズムの解明が必須になる。しかし歯根膜の発生は不明な点が多く、中心的な役割を果たす分子も同定されていない。我々はADAMTSL6βが歯根膜の弾性機能を司るオキシタラン線維の形成を制御していることを明らかにした。そこでADAMTSL6βが歯根膜形成に関わるかを解析するため、ADAMTSL6βを過剰発現するトランスジェニックマウスを作製した。これまでCAG-promoterを用いて歯根膜で強制発現できる事が報告されたので、同じシステムを用いてADAMTSL6βトランスジェニックマウスを作出した。その結果、歯根膜でADAMTSL6βの過剰発現が確認され、マイクロフィブリルの主成分であるfibrillin-1線維の形成促進が観察された。また、その結果として歯根膜の弾性機能であるオキシタラン線維の形成も有意に増加することが観察された。次に全身に及ぼす影響を解析したところ、大動脈においてもADAMTSL6βの過剰発現が確認され、fibrillin-1線維形成の促進に伴う弾性板の増加が観察された。しかし短小化も観察されたため、マイクロCT解析を行ったところ、骨組織の短縮化が観察され、骨格形成阻害が起きている事が判明した。以上の結果より、CAG-promoterシステムを用いれば、歯根膜内での遺伝子機能解析が可能なtransgenic miceの作出が可能であることが示された。またADAMTSL6βは歯根膜のみならず結合組織全般においてマイクロフィブリル形成を誘導していることが示された。

  32. Development of the basic technology for tooth regenerative therapy system

    TSUJI Takashi, KUBOLKI Takuo, KASUGAI Shohei, TOMOOKA Yasuhiro, YAMAMOTO Teruko, SONOYAMA Wataru, SAITO Masahiro

    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: Tokyo University of Science

    2008 - 2010

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    In current research on whole-tooth regenerative therapy, a basic strategy is being pursued in which a bioengineered tooth germ is induced to develop into a fully functional tooth. We developed a three-dimensional organ-germ culture method for the reconstitution a bioengineered organ germ. We successfully demonstrated that our bioengineered tooth germ could develop a fully functioning tooth, which has hardness for masticatory potential, the functional responsibility against a mechanical stress, and perceptive potentials of neural fibers. Furthermore, we demonstrated a further development in this regard in which a bioengineered tooth unit comprising mature tooth, periodontal ligament and alveolar bone, was successfully transplanted into a properly-sized bony hole in the alveolar bone through bone integration by recipient bone remodeling in a murine transplantation model system. These results showed that the bioengineered tooth germ and mature tooth unit could regenerate a fully functioning tooth and an organ replacement regenerative therapy might be feasible.

  33. KK-Periomeデータベースを用いた新規歯周病創薬ターゲットの網羅的探索

    齋藤 正寛

    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: 大阪大学

    2007 - 2009

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    本研究では、歯根膜の発生および再生に関わる分子群の全貌を明らかにするために、ヒト歯根膜遺伝子発現プロファイリングデータベースを作製し、同データベースより歯根膜発生に関わる機能分子を網羅的にスクリーニングした。その結果、f-spondinが歯根膜の発生原基である歯小嚢に特異的に発現することを見出した。f-spondinの発現パターンを解析すると、発生期歯胚の歯小嚢で高発現するが、歯小嚢が歯根膜に分化するとその発現は明らかに低下した。そこでf-spondinの機能解析を行う目的に、培養ヒト歯根膜細胞にf-spondinを過剰発現させ、歯根膜細胞分化に及ぼす影響を解析した。歯根膜はコラーゲン線維に富む結合組織であることから、コラーゲン線維の主成分であるI型コラーゲンならびにコラーゲン線維形成を調整するXII型コラーゲンの遺伝子発現レベルをrealtime PCRで定量した。その結果、f-spondinを過剰発現しているヒト歯根膜細胞ではI型ならびにXII型コラーゲンの遺伝子発現が顕著に低下することが確認された。次にshRNAiを用いてヒト歯根膜細胞においてf-spondin遺伝子発現を挿制したところ、I型ならびにXII型コラーゲンの遺伝子発現の増加が認められた。この結果より、f-spondinはコラーゲン線維形成に関わる遺伝子発現を抑制することから、同分子が歯根膜細胞分化を抑制している可能性が示唆された。そこで免疫不全マウスへの皮下移植実験による分化誘導系を用いて、f-spondinを過剰発現させたヒト歯根膜細胞の分化能力を判定した。一ヶ月移植後に移植片を摘出し、歯根膜細胞の分化マーカーであるtenascin-Nの発現を解析した。その結果、F-spondinを過剰発現させたヒト歯根膜細胞移植片では、tenascin N発現が顕著に低下していることが判明した。以上の結果よりF-spondinは歯小嚢において、歯根膜細胞分化を抑制する因子であることが示された。今後はf-spondinの歯小嚢発生に及ぼす影響を解析し、歯根膜発生おける機能を解明していく予定である。

  34. トランスレーショナルリサーチによる歯根膜弾性線維の機能解明への画期的アプローチ

    須田 直人, 斉藤 正寛

    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: 東京医科歯科大学

    2007 - 2008

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    本研究では、歯根膜組織の恒常性維持や歯周疾患の発症・進展における弾性線維の働きを明らかにすることを目的とする。そこで、1.弾性線維の構成タンパクであるフィブリリン1の遺伝子変異を伴うマルファン症候群患者より単離した歯根膜細胞の解析、2.マルファン症候群のモデルマウス(MgΔ)に歯周病原菌(P.g)を感染させた歯周疾患モデルの解析、の2点を中心に研究を行ってきた。 1. 弾性線維の構成タンパクであるフィブリリン1の遺伝子変異を伴うマルファン症候群患者より単離した歯根膜細胞の解析 疾患患者由来にみられたN2144Sという変異を持つ歯根膜細胞をSCIDマウス背側皮下に移植した結果、microfibril assemblyや細胞の局在に異常がみられることを研究計画初年度の成果として報告した。興味深いことにこれらの異常は、ホスト側の血管近傍では見られなかった。すなわち、血管由来の何らかの因子が変異フィブリリン1の機能を補償する可能性が考えられ、現在この因子の解析や同定を行っている。 2. マルファン症候群のモデルマウス(MgΔ)に歯周病原菌(P.gingivalis)を感染した歯周疾患モデルの解析 MgΔマウスに歯周病原菌を感染させ8週間後に観察すると、野生型マウスと比較して明らかな歯槽骨吸収が観察された。この重篤化にTGF-βシグナルが関与しているのではないかと考え、シグナル阻害剤剤であるテルミサルタンによる抑制効果を解析中である。

  35. Transcriptional regulation of BSP gene mediated by cementoblast like cell in vitro

    YAMAUCHI Masato, NOZAKI Naohito, MATSUZAWA Mituhiro, SAITO Masahiro

    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: Kanagawa Dental College

    2007 - 2008

  36. Possible involvement of sulfation of heparan sulfate proteoglycan in tooth regeneration.

    YAMASHIRO Takashi, SAITO Masahiro, KAMIOKA Hiroshi, HARADA Hidemitsu

    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: Okayama University

    2007 - 2008

  37. 間葉系細胞移植による新規根管治療技術の開発

    寺中 敏夫, 齋藤 正寛

    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: 神奈川歯科大学

    2006 - 2007

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    今日の歯内療法においても根尖孔の骨性瘢痕治癒を積極的に図る方法は未だに確立されていない。一方で,歯科領域において間葉系細胞移植による硬組織再生医療が可能となりつつあり,また,マウスの歯の再生技術も報告され,歯の各構造における発生機構に基づいた歯科再生医療技術の開発なされている。本研究では歯の発生機構の解析による歯髄,歯周組織の再生療法を利用した根尖孔の骨性瘢痕治癒の基礎的検討を試みた。 19年度の研究の結果,in vivoにおいてマウス間葉系細胞由来の歯乳頭細胞中には,象牙質特異的遺伝子Dentin sialoprotein(DSP)発現を有する象牙芽細胞前駆体が存在し,さらに,basic fibroblast growth factor(bFGF)を添加することによりDSPの発現が増強したことから,bFGFは象牙芽細胞分化誘導因子であることを報告した。また,歯根膜前駆体細胞が存在する歯小嚢細胞から,腱/靭帯形成関連遺伝子が高発現し,歯根膜様構造物を形成する単細胞クローンの採取に成功した。さらに,腱/靭帯マーカー遺伝子であるScleraxis(Scx)が成熟した歯根膜のみに発現することを確認し,過剰発現させた同細胞とフィブリン塊を免疫不全マウスに皮下移植すると石灰化物形成能力が抑制され,規則正しい細胞配列を示す歯根膜様構造物の形成が観察されたことから,Scxは石灰化抑制を介して歯根膜内の区画維持に働く可能性が示唆された。 以上の研究成果から,根尖部に象牙芽細胞前駆体細胞,セメント芽細胞および歯根膜前駆体細胞を誘導することができる可能性が強く示唆され,根尖の骨性瘢痕治癒を積極的に促す治療法開発の端緒となすことができた。

  38. Regeneration of resorbed tooth roots by cementogenesis

    SUDA Naoto, YAMAGUCHI Akira, MURAKAMI Shinya, YAMADA Satoru, KIYONO Tohru, SAITO Masahiro

    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: Tokyo Medical and Dental University

    2006 - 2007

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    Pathological tooth root resorption is frequently seen with infection, trauma and tumor, and also induced by some dental treatments. Prevention of pathological resorption in Permanent teeth is a crucial issue to avoid tooth loss and maintain normal oral function, however, there is no effective approach or management for it, so far. Emdogain gelR is a porcine enamel matrix derivative which can promote periodontal tissue regeneration. Since amelogenin is known as one of the bioactive substances in Emdogain, it is quite interesting to ask whether amelogenin and Emdogain have an inhibitory action on odontoclastic root resorption. To clarify this point; we examined the effect of amelogenin on odontoclast formation, in vitro. Furthermore, rat molars were replanted and the root resorption was induced. Emdogain was treated and the effect, on root resorption was examined, in vivo. Odontoclastic cells were isolated from human deciduous teeth and cultured in the presence of 1α25(OH)2vitaminD3 (Vit. D3). The upper first molars off 6 week-old male rats were extracted, and teeth were left on the bench for 1 hr after periodontal ligaments were removed Each tooth was replanted into the socket Root surfaces of some teeth were treated with Emdogain gelR or emdogain powder mixed with the propylene glycol alginate before the replantation. Rats were sacrificed 7 days after replantation and serial saggital sections were prepared. 1) P172 treatment significantly decreased odontoclastic Dell number in the culture. 2) Numerous root resorption lacunae and odontoclasts were seen on the root surface of replanted teeth. In the experimental group, in which Emdogain gelR or Emdogain powder was applied on roots, values of the odontoclast surface, odontoclast number, and the resorbed dentin and cementum were all significantly lower than those of untreated roots. As conclusion, all these findings suggest that amelogenin and Emdogain inhibit the root resorption, in vitro and in vivo.

  39. Development of periodontal ligament regeneration therapy using novel extracellular matrix

    SAITO Masahiro, TERANAKA Toshio, NOZAKI Naohito, HATA Ryuichiro, KIYONO Tohru

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

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

    2005 - 2007

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    The periodontal ligament (PDL) is a strong connective tissue that surrounds the tooth root, absorbs occlusal forces, and functions as a sense organ. The structure of the PDL is often irreversibly damaged when chronic inflammation in the form of "periodontitis" develops, affecting the periodontium. Although various treatments are available for periodontitis, reliable regeneration of the PDL is not yet possible. A basic understanding of PDL development at the molecular level is required to develop methods to regenerate damaged PDL, since the regeneration process will need to mimic the cellular events of PDL development. However, since the specific marker genes for PDL is not available, molecular mechanisms of PDL development have not yet been clarified. Previously we found that the novel extracellular protein ADAMTSL-4 is specifically expressed in PDL. In the present study, we examined if ADAMTSL-4 involved in the PDL development. Expression patterning analysis revealed that adamts14□ mRNA is strongly expressed in the dental follicle, the origin of the PDL. Immunohistochemical and electron microscopy analysis revealed that oxytalan fibrillar-like localization of ADAMTSL4 in the adult PDL. Overexpression of ADAMTSL4 in PDL cells significantly induced formation of oxytalan fiber-like microfibril assembly, indicating that ADAMTSL4 involved in the formation of oxytalan fiber. Our results suggest that ADAMTSL4□ regulates microfibril assembly of fibrillin-1 during PDL development, and could be a novel therapeutic target for the periodontitis.

  40. シグナル分子を用いた新規象牙質再生医療の開発

    小泉 忠彦, 斎藤 正寛

    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: 神奈川歯科大学

    2005 - 2006

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    象牙質形成機構を解析する目的で、本年度は象牙芽細胞前駆体培養系の確立を試みた。そのため未分化な歯胚細胞が存在するマウス切歯根尖部の歯乳頭組織より象牙芽細胞前駆体(Mouse Dental papilla cells : MDP)の採取を試みた。組織採取後、培養皿上に間葉系細胞の形態を示す細胞のoutgrowthが確認された。次に安定した細胞株を作製するためMDPの細胞不死化を試みた。MDPの不死化にはヒトパピローマウイルス16型E6遺伝子のPDZ結合モチーフ欠損変異体を遺伝子導入し、p53遺伝子の不活性化による寿命延長を試みた。遺伝子導入した結果、MDPの寿命は延長し集団倍加数100以上継代可能な不死化細胞であることが確認された。次にMDPの分化能力を調べるため石灰化誘導培地で長期間培養したところ、高いアルカリフォスファターゼ活性と石灰化物の沈着が観察された。次に象牙芽細胞の分化を確かめるためRT-PCR法で遺伝子発現を観察したところ、骨シアロプロテインおよびオステリックス等の骨芽細胞分化に関わる遺伝子群の発現は観察されたが、象牙質マーカーであるdentin sialoprotein(DSP)の発現は観察されなかった。そこで上皮-間葉系の相互作用を利用して象牙芽細胞への分化誘導を行う目的で、基底膜成分から構成されているマトリゲルを用いて実験を行った。その結果、MDPはマトリゲル上でMDPは象牙芽細胞と類似した紡錘状の形態を示し、さらにDSPを発現する象牙芽細胞に分化する事が確認された。以上の結果より、MDPには象牙芽細胞への分化能力を有する前駆体細胞手段が存在することが明らかにされた。次年度は、象牙芽細胞分化誘導能力を有するシグナル分子の探索をMDPを用いて行うことを予定している。

  41. Characterization of Mallase's Epithelial Rest cell line and development to anti-tooth absorbing therapy.

    TSUNODA Akira, SAITO Masahiro, TERANAKA Toshio, SUDA Naoto

    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: Kanagawa Dental College

    2004 - 2006

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    Mallase's Epithelial Rest cell (MMER) is an ameloblast that lined on a tooth root dentin. MMER found to express enamel protein such as amelogenin, however biological role of this cell is still unclear. Recently amelogenin knockout mice showed progressive tooth root absorption suggesting that enamel protein synthesized by MMER act to inhibit osteoclast activation on the tooth root surface. To investigate a biological role of MMER, we try to establish immortalized MMER cell line. MMER isolated from mice incisor root analog side, and immortalized with human papilloma virus E6 deleted with PDZ domain binding motif (MMER^<E6). MMER^<E6> able to grow more that population doubling 30, while MMER without immortalization stop to divide until population doubling 10. MMER expressed amelogenesis related gene such as enamelin, however no expression of amelogenenin was observed. These data indicated that MMER was successfully isolated, however culture condition that induced ameloblast differentiation should be required for investigating biological role of MMER. On the other hand, we established immortalized mice dental epithelium cells (MDE) isolated form developing tooth germ at postnatal lday. MDE able to differentiate into amelobalst that expressed amelogenesis related genes such as amelogenin, ameloblastin and enamelin. These data indicating that MDE could serve as an experimental model for investigating function of MIMER.

  42. アメロゲニンの持つ歯根吸収抑制作用の臨床応用にむけて

    須田 直人, 斉藤 正寛, 大山 紀美栄, 春日井 昇平, 北原 裕

    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: 東京医科歯科大学

    2004 - 2005

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    odontoclastは同じ吸収系細胞であるosteoclastと異なり、これまでin viroの培養系が報告されていなかった。そこで、我々は吸収期にあるヒト乳歯歯根を用いて酵素処理によって再現性よくodontoclastを単離する系を開発した。 硬組織吸収系細胞の形成誘導を評価するin vitroの実験系として、マウス骨髄培養系や脾臓細胞培養系、また我々が開発した萌出中のマウスの歯と歯周組織を用いた培養系(Suda et al.,Bone,2003)が知られている。これらの培養系で形成される吸収系細胞は象牙質上で培養すると吸収窩を形成し、in vivoで歯根吸収を担うodontoclastやcementoclastと良く似た形質を持つことが知られている。 (1)odontoclastは同じ吸収系細胞であるosteoclastと異なり、これまでin viroの培養系が報告されていなかった。そこで、我々は吸収期にあるヒト乳歯歯根を用いて酵素処理によって再現性よくodontoclastを単離する系を開発した。 (2)エムドゲイン中の生理活性因子であるアメロゲニンの歯根吸収抑制作用の検討を計画した。その結果、アメロゲニンのisoformが硬組織吸収細胞の形成や吸収活性を抑制した。 (3)(2)の抑制はRANKL発現抑制を介していた。

  43. 歯髄に存在する神経提由来間葉系幹細胞の多能性および可塑性の検討

    原田 英光, 斎藤 正寛

    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: 大阪大学

    2003 - 2004

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    歯乳頭細胞歯髄を構成する様々な細胞へと分化するが、歯の発生過程では神経細胞になることはない。しかし、歯乳頭細胞と同じ神経堤由来の細胞の中には、体内の歯胚以外の部分で神経細胞に分化するものもある。加えて歯乳頭には、多分化能を持つ組織幹細胞が存在することも報告されている。そこで、歯乳頭の間葉系幹細胞の神経細胞への分化誘導法について検討した。マウス切歯の組織免疫学的検索により、歯乳頭の未分化間葉細胞よりも分化した象牙芽細胞において神経前駆細胞のマーカーであるnestinや神経栄養因子受容体p75NGFRを発現していた。一方で、骨シアロタンパク(DSP)や骨形成因子(BMP)といった石灰化に関する因子も分化に伴って発現し、アルカリフォスファターゼ活性も上昇する。つまり、歯乳頭の未分化間葉系細胞の象牙芽細胞への分化は、神経前駆細胞の分化と石灰化能を持つ細胞への分化の両面を併せ持つと考えられた。さらに、歯乳頭由来一次培養細胞を用いた検索では、nestin、musashil、p75NGFRといった神経前駆細胞マーカーを発現する細胞は認められたが、DSPは発現していなかった。この一次培養細胞をヒトパピローマウイルスにより寿命延命措置を施した上で、神経前駆細胞を成熟ニューロンへと分化させる上で多くの神経系で必須の転写因子であるmash1を強制的に導入させて神経細胞への分化誘導を試みた。mashi1遺伝子導入細胞は、nestin、musashi1、p75NGFRを導入前と変わらずに発現していたが、成熟ニューロンの分化マチル化剤を用いて細胞を処理した後に同様の実験を行ったが、neurofilamentの発現誘導には至らなかった。以上より、mashi1単独での遺伝子発現では成熟ニューロンへ分化誘導することはできないが、歯乳頭の間葉細胞は神経前駆細胞としての特徴を保持しているが明らかになった。また、同様に歯小嚢細胞にも神経前駆細胞としての性質を保持していることも明らかとなった。

  44. Development of poiodontal regenerative medicine that based on molecular mechanism of cementogenesis.

    SAITO Masahiro, TERANAKA Toshio, KINOSHITA Yukihiko, KIYONO Tohru, KIYONO Hidemitsu

    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: Kanagawa Dental College

    2003 - 2004

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    Dental follicle is originated from cranial facial neural crest and it is believed to contain of progenitors for cementoblasts, periodontal ligament cells and osteoblasts. To analyze the differentiation potential of dental follicle, tooth root dentin with cementum and dental follicle are removed from developing tooth germ to be transplanted into the subcutaneous tissue of severe combined immunodeficiency(SCID) mice. After four-week transplantation, extensive amount of cementum matrix was formed between root dentin and dental follicle in the transplant. The newly formed cementum was became almost 20 folds ticker than the previously deposited cementum on root surface, and it was strongly positive for anti-cementum derived attachment protein monoclonal antibody. These results indicated that the cementoblast progenitors were presented in dental follicle, and they are able to differentiate into cementoblast on root surface. Transplantation study of the dental follicle provides a useful model for investigating molecular mechanisms of cementogenesis. On the other hand, novel extracellular matrices have been identified by transcriptome analysis. Among these, a novel extracellulra matrix(ECM) that expressed in tendinous tissue was found to be expressed in the mice periodontal ligament. Immunohictochemical analysis showed that novel ECM found to form microfibril-like structure which is resembled with oxytalan fiber in the periodontal ligament. Aldehyde fuchusin staining analysis demonstrated that distribution of oxytalan fiber was agreement with those of novel ECM. These findings suggested that novel ECM is a new component that consist oxytalan fiber, and may use as a candidate molecule for the regenerative medicine of periodontal disease.

  45. Establishment of regeneration therapy for periodontium based on the molecular mechanisms of cementogenesis

    SAITO Masahiro, TSUNODA Akira, YAMAUCHI Masato, KIYONO Thoru

    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: Kanagawa Dental College

    2001 - 2002

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    Dental follicle is the fibrous tissue that surrounds the developing tooth germ, and it is believed to contain progenitors for cementoblasts, periodontal ligament cells and osteoblasts. To investigate mechanisms of cementogenesis, bovine dental follicle cells (BDFC) were obtained from bovine tooth germs In culture, BDFC exhibited low levels of alkaline phosphatase activity and expressed mRNA for osteopontin (OP) and type I collagen (COLI), as well as low levels of osteocalcin (OC) mRNA. To elucidate the differentiation capacity of BDFC in vivo, cells were transplated into severe combined immunodeficiency (SCID) mice and analyzed after 4 weeks. Transplanted BDFC formed fibrous tissue and cementum-like matrix, which stained positive for anti-cementum attachment protein (CAP) monoclonal antibody (3G9), and expressed mRNA for OC, OP, COLI and bone sialoprotein (BSP). These results indicate that cementoblast progenitors are present in BDFC. To further analysis of cementoblast progenitor, attempt was made to immortalize BDFC. BDFC was immortalized by combination of human papilloma virus type 16 E6E7 and telomerase reverse transcriptase subunit (hTERT) with retrovirus transfer. After gene transfer, BDFC was successfully immortalized, they retained same morphology and cell proliferating activity even when the cells prolonged culture up to PD100. From these findings, cementoblast progenitor cell line seems to isolate from immortalize BDFC. To achieve this goal, we will plan to establish cementoblast progenitor cell line using single cell based analysis.

  46. Development of Regenerative technologies for Periodontitis based on Human Recombinant Protein Expression System

    SAITO Masahiro, YAMAUCHI Masato, TSUNODA Akira, SUZUKI Motoshi, SASAKURI Kenichi

    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: Kanagawa Dental College

    2000 - 2001

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    Cementum is the calcified outer layer through which collagen fibers of connective tissue are anchored into tooth root surfaces. The attachment of connective tissue to root surface is compromised when the cementum is affected by periodontitis, a chronic inflammatory disease, and this can result in irreversible damage to the periodontium. Clinically, the regeneration of cementum is crucial to restore connective tissue attachment because diseased root surface cannot promote attachment and migration of periodontal ligament cells. However, despite many novel approaches available for this purpose, so far it has not been possible to predictably form new cementum. To develop effective material for periodontal regeneration, cementum matrix protein is necessary to recruit the cells which are essential for development and formation of cementum and periodontal ligament and influence their biological activities. Bone sialoprotein is a phosphorylated glycoprotein found in the cementum matrix. During cementogenesis, it is expressed in cementoblasts, and interaction between the cementoblasts and BSP may be critical for cementum formation. With the recent development of recombinant DNA technology, human protein that were normally available due to exceedingly small amount being able to produce for basic research as well as clinical application. In order to improve the regenerative technologies of periodontium, we produced recombinant human BSP (rhBSP). rhBSP with his_6 fusion peptide was expressed in insect cells using a baculovirus expression system, and purified by metal-affinity column chromatography. Purified rhBSP migrated as discrete bands of 60 kDa and 65 kDa in an SDS PAGE and Western blotting. Bovine dental follicle cells, which contain cementoblast progenitors, adhered to the dish surface when it was coated by rhBSP. These results indicate that the baculovirus expression system is useful in producing functional rhBSP, and that the rhBSP may develop the novel regenerative technologies of periodontium.

  47. 歯周組織再生に関する研究:セメント質形成機構の分子生物学的解明

    斎藤 正寛

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 奨励研究(A)

    Institution: 神奈川歯科大学

    1999 - 2000

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    前年度までにセメント質細胞接着因子が(CAP)のモノクローナル抗体を作製し、CAPが歯胚中のセメント質およびセメント芽細胞に限局して存在することを見出してきた。またCAPは歯胚中で65kDaの蛋白質として存在し、歯小嚢細胞に対して細胞接着活性を示すことからセメント質形成のマーカー分子になる可能性も示唆した(現在投稿中)。今年度はCAPの発生過程のprocessingを調べる目的で、歯胚中と永久歯に存在するCAPの分子量を比較検討した。結果はCAPが歯胚中で65kDaの分子量として合成され、永久歯では56kDaに分子量が変化することを明らかにした。またCAPの蛋白質濃度は歯胚から永久歯へ成熟する過程で減少することからも、CAPはセメント質形成の初期過程に関与するマトリックスで、成熟過程において修飾を受け56kDa formとしてセメント質に存在することが示唆された。また65kDaCAPが従来報告されてきたようにコラーゲン様蛋白質であるか否かを調べるために、細菌性コラゲナーゼで処理したところ65kDa CAPが完全に消化されることが認められた。これらの結果より、CAPはコラーゲン性蛋白質でセメント質の形成過程で修飾を受けることが判明した。次にCAPの構造を決定するために、再度CAPの精製の効率化を試みるため、歯胚を酢酸とグアニジン塩酸を用いて蛋白質を抽出し、この可溶性画分をDEAE Sephacel,Q-Sepharose,Mono-Qと3種類の異なる陰イオン交換樹脂を用いて精製を行った。この方法により>1μgのCAP精製に成功した。現在は得られたCAPの内部アミノ酸配列の解析を実行中である。また一部得られたアミノ酸配列を基にウシ歯胚よりRNAを抽出し3'RACE cloningを行ない、cDNA配列の解析も試みている。今後はCAPのcDNA cloningを目的に、歯小嚢細胞からセメント芽細胞の分化誘導を行ない、CAPのcDNA cloningを効率よく行えるlibralyの作製を試みる予定である。

  48. セメント質中に存在する細胞外マトリックスの菌根膜細胞に対する影響

    斎藤 正寛

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 奨励研究(A)

    Institution: 神奈川歯科大学

    1997 - 1998

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    セメント質由来細胞接着因子(CAP)はセメント質に存在するコラーゲン様細胞接着因子でとして報告してきた。平成9年度の実験結果よりCAPは歯肉線維芽細胞とα5β1 integrinと介して接着し、分子量125〜130kDa,80kDa,75kDaおよび44kDaの細胞質内蛋白質のチロシンリン酸化を誘導することを示した。平成10年度の実験結果より、125〜130kDaの蛋白質はfocal adhcsion kinase(FAK)およびp130^<Cas>で主にfocal adhesion kinaseがチロシンリン酸化されており、44kDaはp44 ERK-2mitogen activated protein kinase(MAPK)がそれぞれチロ ・シンリン酸化されていることを同定した。またCAPに接着した細胞はc-fos mRNAの発現が誘導された。これらことからCAPはintegrinを介してFAK-MAPKを経由して核内へ情報を伝達していることが考えられる。CAPに接着しない細胞、または単層の細胞へCAPを加えても顕著な情報伝達物質の活性化は見られないため、CAPは細胞接着を介してのみ情報伝達経路を活性化するとことが確認された。CAPによって誘導されるMAPKのkineticsおよびc-fos mRNAの発現量は、同じα5β1 integrinと結合するfibronectinと比較して異なるため、特有の経路を活性化している可能性が示唆できる。CAPに接着、伸展した細胞内ではb1 integrinおよびvinculinの集積によるfocal contactが存在し、actin stress fiberの重合が観察された。以上の結果より、CAPが誘導する細胞内情報伝達経路はintegrinを介して細胞増殖、分化および細胞骨格形成を制御していることが確認された。またCAPは歯周組織再生時に細胞を選択し、その後細胞増殖および分化を誘導する因子と考えられる。

  49. Study on The Dentinal Native Non-collagenous Protease

    TERANAKA Toshio, SAITO Masahiro, SATOYOSHI Masanori, MUKAI Yoshiharu

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

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

    Institution: Kanagawa Dental College

    1991 - 1993

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    The objectives of this research project were 1) to extract the non-collagenous dentin protein hydrolyzable protease from dentin, 2) to study the hydrolytic ability of the protease against the dentin proteins and proteoglycans, 3) to establish the mineralizing cell culture and 4) to investigate the influence of different dentin adhering mechanisms on shear and fatigue bond strength. The results obtained were as follows : 1.Several proteases were extracted from human and bovine dentin. The approximate molecular weight of 59KDa (59K P-ase) showed the major enzymatic activity and its optimum pH was 9.59K P-ase was inhibited by EDTA and TIMP, and cleaved osteopontin. It was suggested that 59K P-ase is a phophoprotein protease and play an important role in both dentin matrix development and degradation process. 2.Both the EDTA and guanidium chloride extracted dentin proteoglycans were degraded into small fragments by 59K P-ase. It was conceivable that the 59K P-ase was one of metalloproteases but not a collagenase, and play an important role in the process of mineralization and maturation of dentin. 3.Several dentin proteoglycans were obtained, ther molecular weights were 150-180KD, 300KD, 130-150KD and 180-210KD on SDS/PAGE.59K P-ase degraded all of these proteoglycans. E-ext proteoglycan has several core proteins which were stained blue with Stains-all and these core proteins were also cleaved by 59K P-ase. These results demonstrate that the 59K P-ase has a stromelysin-like activities. 4.Odontoblast derived from bovine incisors was cultured on a reconstituted gel of basement membrane components, produced a dentin-specific protein phosphopholyn and grew mineralized nodules. The highest concentration of the enzyme related in the matrix was observed between day 22 and day 36 coinciding with the initiation of mineralization. The described sequence of developmental expression of proteins in this mineralizing dentin cell culture is very similar to that in bone which suggests common mechanisms of matrix mineralization in bone and dentin. The shear and fatigue shear bond strength of a third generational dentin bonding agent (KB-110) was compared with a conventional one. KB-110 showed significantly higher shear and fatigue bond strength than conventional, though its fatigue strength decreased rapidly as the storage period prolonged. These results suggest that the fatigue strength reflects more accurately the retentive properties of the dentin matrix than the shear bond strength.

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