Details of the Researcher

PHOTO

Akihiro Hosoya
Section
Graduate School of Dentistry
Job title
Professor
Degree
e-Rad No.
70350824

Research History 7

  • 2025/08 - Present
    Tohoku University Graduate School of Dentistry

  • 2020/04 -
    Health Sciences University of Hokkaido

  • 2017/04 -
    Health Sciences University of Hokkaido　School of Dentistry

  • 2009/11 -
    Matsumoto Dental University

  • 2007/04 -
    Matsumoto Dental University

  • 2001/11 -
    Matsumoto Dental University

  • 2001/07 -
    Niigata University　Faculty of Dentistry

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Education 2

  • Niigata University

    2001/03 -

  • Niigata University　Faculty of Dentistry

    1997/03 -

Professional Memberships 7

  • 日本口腔ケア学会

    2021/04 -

  • 日本口腔科学会

    2021/04 -

  • JAPANESE ASSOCIATION OF REGENERATIVE DENTISTRY

  • 日本骨代謝学会

  • 日本歯科保存学会

  • 日本解剖学会

  • 歯科基礎医学会

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Research Interests 4

  • 歯髄幹細胞

  • 象牙質再生

  • 象牙芽細胞

  • Pulp calcification

Research Areas 2

  • Life sciences / Oral medicine /

  • Life sciences / Anatomy /

Awards 2

  1. 歯科基礎医学会賞（第51回歯科基礎医学会総会）

    2009

  2. デンツプライ賞（第125回日本歯科保存学会秋期大会）

    2007

Papers 115

  1. Genetic profile of Lepr+ skeletal stem/progenitor cells in the periodontal ligament and functional compensation during aging and bone repair. International-journal

    Satsuki Shidara, Shinichirou Ito, Karishma Desai, Akihide Tokuyama, Ran Leng, Mana Kawakami, Satoru Matsunaga, Toshihisa Komori, Akihiro Hosoya, Yasushi Nishii, Toshihide Mizoguchi

    Bone　206　117833-117833　2026/02/13

    DOI： 10.1016/j.bone.2026.117833 　

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    Skeletal stem/progenitor cells (SSPCs) play a fundamental role in maintaining skeletal homeostasis throughout life. Leptin receptor (Lepr)-positive cells were initially identified as SSPCs in the long bone marrow and later in the craniofacial skeleton, where they localize within the periodontal ligament (PDL), particularly among fibroblastic cells (PDLCs). However, their hierarchical organization, maintenance of stemness, and relationships with other SSPC populations remain poorly understood. Through lineage tracing and single-cell RNA sequencing facilitated by Runx2-GFP expression, we identified a Lepr+ subpopulation characterized by Thy1 expression but lacking Runx2, which is hierarchically positioned at the apex of the Lepr+ PDLC lineage and gives rise to downstream osteogenic progeny. However, their SSPC capacity to contribute to osteocytes and cementocytes is quantitatively limited and declines with age, and this contribution may exhibit sexual dimorphism. At the single-cell transcriptome level, Lepr+ PDLCs shared an expression profile with long bone-derived Lepr+ SSPCs; however, the expression of Kit ligand (Kitl) was uniquely restricted to Lepr+ cells within the PDLCs. In contrast, they were not enriched for other PDLC-associated SSPC markers, such as Axin2, Gli1, and Acta2. Although Lepr+ PDLCs contributed to bone regeneration by differentiating into osteocytes after tooth extraction, their contribution was limited. Moreover, genetic ablation of Lepr+ PDLCs did not reduce the regenerated bone volume, suggesting compensatory contributions from other SSPC populations. Collectively, these findings reveal a previously unrecognized hierarchical and functional organization of Lepr+ PDLCs and demonstrate that their contribution to skeletal homeostasis progressively declines with age, with potential compensation by other SSPC populations.

  2. Relationship between localization of annexins and dentinogenesis during rat tooth development

    Toru Shibui, Akihiro Hosoya, Masami Takahashi, Hiroaki Takebe, Shunichi Shibata, Kazuharu Irie

    The Anatomical Record　2025/08/29

    Publisher: Wiley

    DOI： 10.1002/ar.70043 　

    ISSN： 1932-8486

    eISSN： 1932-8494

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    Abstract Annexins (ANXAs) are a calcium‐dependent, membrane‐bound protein superfamily involved in the transport of matrix vesicle ion channels and Ca2+ ions, which are essential for early hard tissue calcification. However, the localization of ANXAs in dentin calcification is unknown. To analyze the localization and function of ANXA1, 2, 5, and 6 in odontoblast differentiation and dentin calcification, we examined the immunohistochemical localization of ANXAs in developing rat molars. During the bud (E15) and cap (E17) stages, ANXA‐positive cells were not observed in the dental mesenchyme or dental papillae. In the early bell stage (E20), many ANXA1‐, 2‐, 5‐, 6‐, and CD31‐positive cells were observed around the blood vessels of the dental papillae. In the late bell stage (P2), CD31, ANXA1, and ANXA2 immunoreactivity was observed around blood vessels in the vicinity of odontoblasts, but little ANXA5 and ANXA6 immunoreactivity was observed. ANXA2 immunoreactivity was observed in the cytoplasm and plasma membrane of the odontoblast. Furthermore, the immunoreactivity of plasma membrane calcium‐ATPase (PMCA‐ATPase), one of the Ca2+ ion efflux systems in odontoblasts, was observed to be co‐localized with ANXA2. On postnatal Day 7 (P7), PMCA‐ATPase immunoreactivity in odontoblasts decreased compared with P2. At P7 and 5 weeks of age (P35), little immunoreactivity for ANXAs was observed in odontoblasts and perivascular areas close to odontoblasts. ANXA1‐, 2‐, 5‐, and 6‐positive cells may be involved in vascular induction in the developing dental papillae, and ANXA2 may be involved in early dentin calcification.

  3. 苦味受容体TAS2R38の舌癌切除標本における発現の検討

    志茂 剛, 高畠 清文, 堀江 尚弘, 細矢 明宏, 長塚 仁, Nasrun Nisrina Ekayani

    日本口腔科学会雑誌　74　(2)　129-129　2025/07

    Publisher: (NPO)日本口腔科学会

    ISSN： 0029-0297

    eISSN： 2185-0461

  4. Loss of integrin alpha7-mediated signaling induces a dendritic cell-like phenotype in macrophages cultured on laminin-211/221 isoforms. International-journal

    Nagako Yoshiba, Tomoki Maekawa, Kiyotoshi Sekiguchi, Masaru Kaku, Kridtapat Sirisereephap, Meircurius Surboyo, Yurie Sato-Yamada, Andrea Rosenkranz, Akihiro Hosoya, Naoto Ohkura, Yoshito Kakihara, Takeyasu Maeda, George Hajishengallis, Kenji Izumi, Kunihiko Yoshiba

    The Journal of biological chemistry　110419-110419　2025/06/25

    DOI： 10.1016/j.jbc.2025.110419 　

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    Laminin comprises α/β/γ subunits and performs tissue-specific functions that control cellular behavior. Laminin-α2 chains are highly expressed in neural components such as glial and Schwann cells and in muscles. Macrophages play important roles in tissue homeostasis and repair, and laminins affect macrophage dynamics. Integrin α7, a transmembrane receptor crucial for regulating cell-matrix interactions, has a high affinity for laminin-α2, but its function in macrophages remains unknown. Here, we find that loss of integrin α7 signaling induces a dendritic cell (DC)-like phenotype in THP-1-derived macrophages and in primary monocytes-derived macrophages (MDMs) induced by granulocyte macrophage colony-stimulating factor (GM-CSF) cultured on laminin-α2 chains. Functional blocking of integrin α7 induced dendritic processes of THP-1-derived macrophages. Gene expression analysis revealed DC markers and costimulatory molecules, and coculture experiments demonstrated that the DC-like cells could stimulate T cell proliferation. Functional inhibition of integrin α7 decreased PI3K-p85α levels and activated PI3K, thereby activating AKT. MDMs cultured on laminin α2 chains decreased integrin α7 expression, exhibited dendritic-like morphology, and increased expression of DC markers and costimulatory molecules. These findings suggest that, besides the established influence of cytokine milieu, DC differentiation is regulated by laminin α2/integrin α7-mediated cell adhesion. Integrin α7 has been a therapeutic target in tumors, and antibody-based integrin α7 neutralization can be clinically useful. The results of this study suggest implications for integrin α7 and laminin-α2 chains in DC immunotherapy.

  5. Involvement of α-Smooth Muscle Actin-Positive Cells in Bone Regeneration Induced by Rib Fractures

    Hiroaki Takebe, Toru Shibui, Tsuyoshi Shimo, Akihiro Hosoya

    Journal of Hard Tissue Biology　34　(3)　165-170　2025

    Publisher: Society for Hard Tissue Regenerative Biology

    DOI： 10.2485/jhtb.34.165 　

    ISSN： 1341-7649

    eISSN： 1880-828X

  6. Polycomb protein Bmi1 promotes odontoblast differentiation by accelerating Wnt and BMP signaling pathways. International-journal

    Akihiro Hosoya, Hiroaki Takebe, Yuri Seki-Kishimoto, Yukiko Noguchi, Tadashi Ninomiya, Akira Yukita, Nagako Yoshiba, Ayako Washio, Masahiro Iijima, Takahiko Morotomi, Chiaki Kitamura, Hiroaki Nakamura

    Histochemistry and cell biology　163　(1)　11-11　2024/11/26

    DOI： 10.1007/s00418-024-02337-2 　

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    Bmi1 is a polycomb protein localized in stem cells and maintains their stemness. This protein is also reported to regulate the expression of various differentiation genes. In this study, to analyze the role of Bmi1 during dentinogenesis, we examined the immunohistochemical localization of Bmi1 during rat tooth development as well as after cavity preparation. Bmi1 localization was hardly detected in the dental mesenchyme at the bud and cap stages. After the bell stage, however, this protein became detectable in preodontoblasts and early odontoblasts just beginning dentin matrix secretion. As dentin formation progressed, Bmi1 immunoreactivity in the odontoblasts decreased in intensity. After cavity preparation, cells lining the dentin and some pulp cells under the cavity were immunopositive for Bmi1 at 4 days. Odontoblast-like cells forming reparative dentin were immunopositive for Bmi1 at 1 week, whereas their immunoreactivity was not detected after 8 weeks. We further analyzed the function of Bmi1 using KN-3 cells, a dental mesenchymal cell line. Overexpression of Bmi1 in KN-3 cells promoted mineralized tissue formation. In contrast, siRNA knockdown of Bmi1 in KN-3 cells reduced alkaline phosphatase activity and the expression of odontoblast differentiation marker genes such as Runx2, osterix, and osteocalcin. Additionally, KN-3 cells transfected with siRNA against Bmi1 showed reduced nuclear transition of β-catenin and expression of phosphorylated-Smad1/5/8. Taken together, these findings suggest that Bmi1 was localized in the odontoblast-lineage cells in their early differentiation stages. Bmi1 might positively regulate their differentiation by accelerating Wnt and BMP signaling pathways.

  7. Localization of α-smooth muscle actin in osteoblast differentiation during periodontal development. International-journal

    Hiroaki Takebe, Hanaka Sato, Toshihide Mizoguchi, Akihiro Hosoya

    Cell and tissue research　2024/11/23

    DOI： 10.1007/s00441-024-03940-4 　

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    α-Smooth muscle actin (α-SMA) is an actin isoform commonly found within vascular smooth muscle cells. Moreover, α-SMA-positive cells are localized in the dental follicle (DF). DF is derived from alveolar bone (AB), cementum, and periodontal ligament (PDL). Therefore, α-SMA-positive cells in the periodontal tissue are speculated to be a marker for mesenchymal stem cells during tooth development. In particular, the mechanism of osteoblast differentiation is not clear. This study demonstrated the fate of α-SMA-positive cells around the tooth germ immunohistochemically. First, α-SMA- and Runx2-positive localization at embryonic days (E) 13, E14, postnatal days (P) 9, and P15 was demonstrated. α-SMA- and Runx2-positive cells were detected in the upper part of the DF at P1. At P9 and P15, α-SMA-positive cells in the PDL were detected in the upper and lower parts. The positive reaction of Runx2 was also localized in the PDL. Then, the distribution of α-SMA-positive cell progeny at P9 and P15 were clarified using α-SMA-CreERT2/ROSA26-loxP-stop-loxP-tdTomato (α-SMA/tomato) mice. It has known that Runx2-positive cells differentiate into osteoblasts. In this study, some Runx2 and α-SMA-positive cells were localized in the DF and PDL. The lineage-tracing analysis demonstrated that the α-SMA/tomato-positive cells expressing Runx2 or Osterix were detected on the AB surface at P15. α-SMA/tomato-positive cells expressing type I collagen were found in the AB matrix. These results indicate that the progeny of the α-SMA-positive cells in the DF could differentiate into osteogenic cells. In conclusion, α-SMA could be a potential marker of progenitor cells that differentiate into osteoblasts.

  8. Osteoblast differentiation of Gli1⁺ cells via Wnt and BMP signaling pathways during orthodontic tooth movement. International-journal

    Yuri Seki, Hiroaki Takebe, Yuya Nakao, Kohei Sato, Toshihide Mizoguchi, Hiroaki Nakamura, Masahiro Iijima, Akihiro Hosoya

    Journal of oral biosciences　2024/03/16

    DOI： 10.1016/j.job.2024.03.004 　

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    OBJECTIVES: Factors that induce bone formation during orthodontic tooth movement (OTM) remain unclear. Gli1 was recently identified as a stem cell marker in the periodontal ligament (PDL). Therefore, we evaluated the mechanism of differentiation of Cre/LoxP-mediated Gli1/Tomato+ cells into osteoblasts during OTM. METHODS: After the final administration of tamoxifen to 8-week-old Gli1-CreERT2/ROSA26-loxP-stop-loxP-tdTomato mice for 2 days, nickel-titanium closed coil springs were attached between the upper anterior alveolar bone and the first molar. Immunohistochemical localizations of β-catenin, Smad4, and Runx2 were observed in the PDL on 2, 5, and 10 days after OTM initiation. RESULTS: In the untreated tooth, few Gli1/Tomato+ cells were detected in the PDL. Two days after OTM initiation, the number of Gli1/Tomato+ cells increased in the PDL on the tension side. On this side, 49.3 ± 7.0% of β-catenin+ and 48.7 ± 5.7% of Smad4+ cells were found in the PDL, and Runx2 expression was detected in some Gli1/Tomato+ cells apart from the alveolar bone. The number of positive cells in the PDL reached a maximum on day 5. In contrast, on the compression side, β-catenin and Smad4 exhibited less immunoreactivity. On day 10, Gli1/Tomato+ cells were aligned on the alveolar bone on the tension side, with some expressing Runx2. CONCLUSIONS: Gli1+ cells in the PDL differentiated into osteoblasts during OTM. Wnt and bone morphogenetic proteins signaling pathways may be involved in this differentiation.

  9. メラノーマ骨微小環境におけるソニックヘッジホッグの役割

    平木 大地, Shamsoon Karnoon, 吉田 光希, 高畠 清文, 藤田 尚正, Nasrun Nisrina Ekayani, 長塚 仁, 安彦 善裕, 細矢 明宏, 志茂 剛

    日本口腔科学会雑誌　72　(2)　79-79　2023/07

    Publisher: (NPO)日本口腔科学会

    ISSN： 0029-0297

    eISSN： 2185-0461

  10. The Role of Hedgehog Signaling in the Melanoma Tumor Bone Microenvironment. International-journal

    Karnoon Shamsoon, Daichi Hiraki, Koki Yoshida, Kiyofumi Takabatake, Hiroaki Takebe, Kenji Yokozeki, Naohiro Horie, Naomasa Fujita, Nisrina Ekayani Nasrun, Tatsuo Okui, Hitoshi Nagatsuka, Yoshihiro Abiko, Akihiro Hosoya, Takashi Saito, Tsuyoshi Shimo

    International journal of molecular sciences　24　(10)　2023/05/16

    DOI： 10.3390/ijms24108862 　

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    A crucial regulator in melanoma progression and treatment resistance is tumor microenvironments, and Hedgehog (Hh) signals activated in a tumor bone microenvironment are a potential new therapeutic target. The mechanism of bone destruction by melanomas involving Hh/Gli signaling in such a tumor microenvironment is unknown. Here, we analyzed surgically resected oral malignant melanoma specimens and observed that Sonic Hedgehog, Gli1, and Gli2 were highly expressed in tumor cells, vasculatures, and osteoclasts. We established a tumor bone destruction mouse model by inoculating B16 cells into the bone marrow space of the right tibial metaphysis of 5-week-old female C57BL mice. An intraperitoneal administration of GANT61 (40 mg/kg), a small-molecule inhibitor of Gli1 and Gli2, resulted in significant inhibition of cortical bone destruction, TRAP-positive osteoclasts within the cortical bone, and endomucin-positive tumor vessels. The gene set enrichment analysis suggested that genes involved in apoptosis, angiogenesis, and the PD-L1 expression pathway in cancer were significantly altered by the GANT61 treatment. A flow cytometry analysis revealed that PD-L1 expression was significantly decreased in cells in which late apoptosis was induced by the GANT61 treatment. These results suggest that molecular targeting of Gli1 and Gli2 may release immunosuppression of the tumor bone microenvironment through normalization of abnormal angiogenesis and bone remodeling in advanced melanoma with jaw bone invasion.

  11. Bone formation ability of Gli1+ cells in the periodontal ligament after tooth extraction. International-journal

    Saki Fujii, Hiroaki Takebe, Toshihide Mizoguchi, Hiroaki Nakamura, Tsuyoshi Shimo, Akihiro Hosoya

    Bone　116786-116786　2023/05/08

    DOI： 10.1016/j.bone.2023.116786 　

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    During the process of socket healing after tooth extraction, osteoblasts appear in the tooth socket and form alveolar bone; however, the source of these osteoblasts is still uncertain. Recently, it has been demonstrated that cells expressing Gli1, a downstream factor of sonic hedgehog signaling, exhibit stem cell properties in the periodontal ligament (PDL). Therefore, in the present study, the differentiation ability of Gli1+-PDL cells after tooth extraction was analyzed using Gli1-CreERT2/ROSA26-loxP-stop-loxP-tdTomato (iGli1/Tomato) mice. After the final administration of tamoxifen to iGli1/Tomato mice, Gli1/Tomato+ cells were rarely detected in the PDL. One day after the tooth extraction, although inflammatory cells appeared in the tooth socket, Periostin+ PDL-like tissues having a few Gli1/Tomato+ cells remained near the alveolar bone. Three days after the extraction, the number of Gli1/Tomato+ cells increased as evidenced by numerous PCNA+ cells in the socket. Some of these Gli1/Tomato+ cells expressed BMP4 and Phosphorylated (P)-Smad1/5/8. After seven days, the Osteopontin+ bone matrix was formed in the tooth socket apart from the alveolar bone. Many Gli1/Tomato+ osteoblasts that were positive for Runx2+ were arranged on the surface of the newly formed bone matrix. In the absence of Gli1+-PDL cells in Gli1-CreERT2/Rosa26-loxP-stop-loxP-tdDTA (iGli1/DTA) mice, the amount of newly formed bone matrix was significantly reduced in the tooth socket. Therefore, these results collectively suggest that Gli1+-PDL cells differentiate into osteoblasts to form the bone matrix in the tooth socket; thus, this differentiation might be regulated, at least in part, by bone morphogenetic protein (BMP) signaling.

  12. Immunohistochemical localization of CD146 and alpha-smooth muscle actin during dentin formation and regeneration. International-journal

    Toru Shibui, Akihiro Hosoya, Hiroaki Takebe, Masami Takahashi, Yuri Seki, Saki Fujii, Kazuharu Irie

    Anatomical record (Hoboken, N.J. : 2007)　2023/01/10

    DOI： 10.1002/ar.25155 　

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    Cluster of differentiation 146 (CD146) is known to localize in stem cells and precursor cells of various tissues. In this study, to analyze the function of CD146 in odontoblast differentiation, immunohistochemical localization of CD146 was examined during rat molar tooth development and after cavity preparation. At the cap and bell stages, many CD146-positive cells were visible around the blood vessels in the dental papillae. On Postnatal day 2, osterix-positive odontoblasts were arranged in the dentin sialoprotein (DSP)-positive predentin, and many CD146-positive cells were observed near these odontoblasts with blood vessels. Some perivascular CD146-positive cells overlapped with Smad4-positive cells. However, the immunoreactivity for alpha-smooth muscle actin (α-SMA), one of the markers for undifferentiated cells, was negligible. Furthermore, the number of these cells decreased in the dental pulp on Postnatal day 28. On Day 4 after cavity preparation, Osterix-positive odontoblasts appeared lining the reparative dentin. Most of the blood vessels near the reparative dentin showed immunoreactivities for CD146. Reparative odontoblasts actively formed DSP-positive dentin matrix because these cells were positive for Smad4 and Osterix, but not for α-SMA. After 7 days, the number of CD146-positive cells near blood vessels decreased in the dental pulp beneath the cavity. These results suggest that the CD146 is expressed in the perivascular area of the dental pulp and induces vascularization in the vicinity of dentin formation, and some CD146-positive cells are activated by the bone morphogenetic protein signaling pathway and differentiate into odontoblasts in the early stages of dentin formation and repair.

  13. Immunohistochemical Analysis of CCN2 in Experimental Fracture Healing Models. International-journal

    Tsuyoshi Shimo, Hiroaki Takebe, Saki Fujii, Akihiro Hosoya

    Methods in molecular biology (Clifton, N.J.)　2582　335-342　2023

    DOI： 10.1007/978-1-0716-2744-0_23 　

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    Skeletal fractures are most common large-organ traumatic injuries that impact the functions and esthetic outcomes and quality of life. Unfortunately, infection during the fracture healing process and inadequate blood supply to the bone impede reduced ability to produce cartilage and effective bone callus formation, leading to nonunion or delayed union fracture. Therefore, studying the mechanism of fracture healing is an important task in solving the problem of fracture healing failure. Animal models of bone fracture healing are important tools to investigate the pathogenesis and develop treatment strategies. This protocol introduces researchers to a bone repair model utilizing the ribs of rats and the immunohistological expression of cellular communication network factor/connective tissue growth factor (CTGF/CCN2) during the fracture healing processes.

  14. Differentiation ability of Gli1+ cells during orthodontic tooth movement

    Yuri Seki, Hiroaki Takebe, Toshihide Mizoguchi, Hiroaki Nakamura, Masahiro Iijima, Kazuharu Irie, Akihiro Hosoya

    Bone　116609-116609　2022/11

    Publisher: Elsevier BV

    DOI： 10.1016/j.bone.2022.116609 　

    ISSN： 8756-3282

  15. 抜歯窩治癒過程におけるGli1陽性歯根膜細胞の骨形成能(Osteogenic ability of Gli1-positive cells in periodontal ligament after tooth extraction)

    藤井 彩貴, 建部 廣明, 溝口 利英, 志茂 剛, 細矢 明宏

    Journal of Oral Biosciences Supplement　2022　233-233　2022/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  16. Gli1+-PDL Cells Contribute to Alveolar Bone Homeostasis and Regeneration. International-journal

    N Shalehin, Y Seki, H Takebe, S Fujii, T Mizoguchi, H Nakamura, N Yoshiba, K Yoshiba, M Iijima, T Shimo, K Irie, A Hosoya

    Journal of dental research　220345221106921-220345221106921　2022/07/04

    DOI： 10.1177/00220345221106921 　

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    The periodontal ligament (PDL) contains mesenchymal stem cells (MSCs) that can differentiate into osteoblasts, cementoblasts, and fibroblasts. Nevertheless, the distribution and characteristics of these cells remain uncertain. Gli1, an essential hedgehog signaling transcription factor, functions in undifferentiated cells during embryogenesis. Therefore, in the present study, the differentiation ability of Gli1+ cells was examined using Gli1-CreERT2/ROSA26-loxP-stop-loxP-tdTomato (iGli1/Tomato) mice. In 4-wk-old iGli1/Tomato mice, Gli1/Tomato+ cells were only slightly detected in the PDL, around endomucin-expressing blood vessels. These cells had proliferated over time, localizing in the PDL as well as on the bone and cementum surfaces at day 28. However, in 8-wk-old iGli1/Tomato mice, Gli1/Tomato+ cells were quiescent, as most cells were not immunoreactive for Ki-67. These cells in 8-wk-old mice exhibited high colony-forming unit fibroblast activity and were capable of osteogenic, chondrogenic, and adipogenic differentiation in vitro. In addition, after transplantation of teeth of iGli1/Tomato mice into the hypodermis of wild-type mice, Tomato fluorescence indicating the progeny of Gli1+ cells was detected in the osteoblasts and osteocytes of the regenerated bone. These results demonstrate that Gli1+ cells in the PDL were MSCs and could contribute to the alveolar bone regeneration.

  17. Gli1陽性歯根膜細胞の抜歯窩治癒過程における分化能

    藤井 彩貴, 志茂 剛, 細矢 明宏, 建部 廣明

    日本口腔科学会雑誌　71　(2)　127-127　2022/07

    Publisher: (NPO)日本口腔科学会

    ISSN： 0029-0297

    eISSN： 2185-0461

  18. RANKL/OPG ratio regulates odontoclastogenesis in damaged dental pulp

    Daisuke Nishida, Atsushi Arai, Lijuan Zhao, Mengyu Yang, Yuko Nakamichi, Kanji Horibe, Akihiro Hosoya, Yasuhiro Kobayashi, Nobuyuki Udagawa, Toshihide Mizoguchi

    Scientific Reports　11　(1)　2021/12

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s41598-021-84354-y 　

    eISSN： 2045-2322

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    <title>Abstract</title>Bone-resorbing osteoclasts are regulated by the relative ratio of the differentiation factor, receptor activator NF-kappa B ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG). Dental tissue-localized-resorbing cells called odontoclasts have regulatory factors considered as identical to those of osteoclasts; however, it is still unclear whether the RANKL/OPG ratio is a key factor for odontoclast regulation in dental pulp. Here, we showed that odontoclast regulators, macrophage colony-stimulating factor-1, RANKL, and OPG were detectable in mouse pulp of molars, but OPG was dominantly expressed. High OPG expression was expected to have a negative regulatory effect on odontoclastogenesis; however, odontoclasts were not detected in the dental pulp of <italic>OPG-deficient</italic> (<italic>KO</italic>) mice. In contrast, damage induced odontoclast-like cells were seen in wild-type pulp tissues, with their number significantly increased in <italic>OPG-KO</italic> mice. Relative ratio of RANKL/OPG in the damaged pulp was significantly higher than in undamaged control pulp. Pulp damages enhanced hypoxia inducible factor-1α and -2α, reported to increase RANKL or decrease OPG. These results reveal that the relative ratio of RANKL/OPG is significant to pulpal odontoclastogenesis, and that OPG expression is not required for maintenance of pulp homeostasis, but protects pulp from odontoclastogenesis caused by damages.

  19. 矯正学的歯の移動時に出現する骨芽細胞はGli1陽性歯根膜細胞に由来する

    関 有里, 建部 廣明, 北浦 英樹, 飯嶋 雅弘, 溝口 到, 細矢 明宏

    日本矯正歯科学会大会プログラム・抄録集　80回　151-151　2021/11

    Publisher: (公社)日本矯正歯科学会

  20. 抜歯窩治癒過程におけるGli1陽性歯根膜細胞の分化能(Differential ability of Gli1-positive cells in periodontal ligament after tooth extraction)

    藤井 彩貴, 建部 廣明, 溝口 利英, 志茂 剛, 細矢 明宏

    Journal of Oral Biosciences Supplement　2021　122-122　2021/10

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  21. 抜歯窩治癒過程におけるGli1陽性歯根膜細胞の分化能(Differential ability of Gli1-positive cells in periodontal ligament after tooth extraction)

    藤井 彩貴, 建部 廣明, 溝口 利英, 志茂 剛, 細矢 明宏

    Journal of Oral Biosciences Supplement　2021　122-122　2021/10

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  22. 抜歯窩治癒過程におけるGli1陽性歯根膜細

    藤井 彩貴, 志茂 剛, 細矢 明宏, 建部 廣明

    日本口腔科学会雑誌　70　(2)　125-125　2021/07

    Publisher: (NPO)日本口腔科学会

    ISSN： 0029-0297

    eISSN： 2185-0461

  23. Localization of Bmi1 in osteoblast-lineage cells during endochondral ossification. International-journal

    Hiroaki Takebe, Kazuharu Irie, Akihiro Hosoya

    Anatomical record (Hoboken, N.J. : 2007)　2021/06/08

    DOI： 10.1002/ar.24693 　

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    Encoded by B cell-specific moloney murine leukemia virus integration site 1, Bmi1 is part of the polycomb group of proteins localized in stem and undifferentiated cells. It regulates the expression of various differentiation genes. However, the regulatory mechanism of skeletal development by Bmi1 remains poorly understood. In this study, we aimed to observe Bmi1 distribution during endochondral ossification processes in rat bone development and fracture healing. Immunoreactivity of Bmi1 was detected in the mesenchymal cell aggregation area at embryonic day (E) 14 and in cells around the center of cartilage primordium at E 16. Subsequently, the calcified bone matrix was formed around the cartilage primordium, and osteoblasts expressing Runt-related transcription factor 2 (Runx2) and Osterix (Osx) showed immunopositivity for Bmi1. At 4 days after bone fracture, the connective tissue around the fractured bone contained Bmi1-positive cells. At 42 days after fracture, osteoblasts along the surface of the new bone revealed Bmi1-, Runx2- and Osx-positive reactions, but the Bmi1 immunoreactivity in osteocytes was less than the Runx2 and Osx immunoreactivities. In conclusion, Bmi1 is localized in the osteoblast-lineage cells in their early differentiation stages, and it might regulate their differentiation during endochondral ossification.

  24. Odontoblast death drives cell-rich zone-derived dental tissue regeneration

    Lijuan Zhao, Shinichirou Ito, Atsushi Arai, Nobuyuki Udagawa, Kanji Horibe, Miroku Hara, Daisuke Nishida, Akihiro Hosoya, Rinya Masuko, Koji Okabe, Masashi Shin, Xianqi Li, Koichi Matsuo, Shinichi Abe, Satoru Matsunaga, Yasuhiro Kobayashi, Hideaki Kagami, Toshihide Mizoguchi

    Bone　116010-116010　2021/05

    Publisher: Elsevier BV

    DOI： 10.1016/j.bone.2021.116010 　

    ISSN： 8756-3282

  25. Gli1陽性歯根膜細胞の抜歯窩治癒過程における機能解析

    藤井 彩貴, 関 有里, 建部 廣明, 溝口 利英, 志茂 剛, 細矢 明宏

    日本口腔ケア学会雑誌　15　(3)　162-162　2021/04

    Publisher: (一社)日本口腔ケア学会

    ISSN： 1881-9141

  26. Boric acid inhibits alveolar bone loss in rat experimental periodontitis through diminished bone resorption and enhanced osteoblast formation

    Nazmus Shalehin, Akihiro Hosoya, Hiroaki Takebe, Md Riasat Hasan, Kazuharu Irie

    Journal of Dental Sciences　15　(4)　437-444　2020/12

    Publisher: Elsevier BV

    DOI： 10.1016/j.jds.2019.09.009 　

    ISSN： 1991-7902

  27. Stem cell properties of Gli1-positive cells in the periodontal ligament. International-journal

    Akihiro Hosoya, Nazmus Shalehin, Hiroaki Takebe, Saki Fujii, Yuri Seki, Toshihide Mizoguchi, Tsuyoshi Shimo, Masahiro Iijima, Kazuharu Irie

    Journal of oral biosciences　62　(4)　299-305　2020/12

    DOI： 10.1016/j.job.2020.08.002 　

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    BACKGROUND: The periodontal ligament (PDL), which surrounds the tooth root, contains mesenchymal stem cells (MSCs) capable of differentiating into osteoblasts, cementoblasts, and fibroblasts under normal conditions. These MSCs are thought to have important roles in the repair and regeneration of injured periodontal tissues. However, since there is no useful marker for MSCs in the PDL, the characteristics and distributions of these cells remain unclear. Gli1, an essential hedgehog signaling transcription factor, functions in undifferentiated cells during embryogenesis. Previous studies have demonstrated that the dental epithelial and mesenchymal cells positive for Gli1 in developing teeth have stem cell properties, including the ability to form colonies and pluripotency. Therefore, the focus of this review is the stem cell properties of Gli1-positive cells in the PDL, with an emphasis on the differentiation ability of osteoblasts for the regeneration of periodontal tissues. HIGHLIGHT: Lineage tracing analysis identified Gli1-positive PDL cells as MSCs that contribute to the formation of periodontal tissues and can regenerate alveolar bone. CONCLUSION: Gli1 is a potential stem cell marker in the PDL. A more definitive understanding of the functions of Gli1-positive cells could be useful for the development of regenerative methods using the MSCs in the PDL.

  28. 顎関節への荷重負荷がラット下顎頭軟骨の基質タンパク発現に与える影響

    尾立 卓弥, 中尾 友也, 細矢 明宏, 飯嶋 雅弘

    北海道医療大学歯学雑誌　39　(1)　1-10　2020/06

    Publisher: 北海道医療大学歯学会

    ISSN： 1880-5892

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    咬合挙上による荷重負荷が下顎頭軟骨の細胞ならびに細胞外基質タンパク質の局在に与える影響について検討した。実験動物には生後7週齢のWistar系雄性ラット90匹を用い、未処置群と咬合挙上群に分けた。荷重負荷後の下顎頭におけるアルカリ性ホスファターゼ活性の変化を観察した。またX型コラーゲン、骨基質タンパク質であるオステオポンチン(OSP)ならびにオステオカルシン(OC)の発現と局在を生化学的および免疫組織化学的手法により解析した。OSPおよびOCのmRNA発現は、咬合挙上群1、2、3週後では未処置群と比較して有意な変化はみられなかった。一方、咬合挙上群4週後では未処置群と比較して発現量が有意に上昇した。また、免疫組織化学的局在に関して、未処置群0週、4週では下顎頭の軟骨細胞ならびに軟骨基質ではOSPの陽性反応はみられず、OCの陽性反応も認められなかった。OSP、OCのような非コラーゲン性タンパク質は肥大軟骨細胞層の軟骨小腔周囲の基質に局在することが明らかになった。

  29. Expression and Role of IL-1β Signaling in Chondrocytes Associated with Retinoid Signaling during Fracture Healing. International-journal Peer-reviewed

    Tsuyoshi Shimo, Hiroaki Takebe, Tatsuo Okui, Yuki Kunisada, Soichiro Ibaragi, Kyoichi Obata, Naito Kurio, Karnoon Shamsoon, Saki Fujii, Akihiro Hosoya, Kazuharu Irie, Akira Sasaki, Masahiro Iwamoto

    International journal of molecular sciences　21　(7)　2020/03/29

    DOI： 10.3390/ijms21072365 　

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    The process of fracture healing consists of an inflammatory reaction and cartilage and bone tissue reconstruction. The inflammatory cytokine interleukin-1β (IL-1β) signal is an important major factor in fracture healing, whereas its relevance to retinoid receptor (an RAR inverse agonist, which promotes endochondral bone formation) remains unclear. Herein, we investigated the expressions of IL-1β and retinoic acid receptor gamma (RARγ) in a rat fracture model and the effects of IL-1β in the presence of one of several RAR inverse agonists on chondrocytes. An immunohistochemical analysis revealed that IL-1β and RARγ were expressed in chondrocytes at the fracture site in the rat ribs on day 7 post-fracture. In chondrogenic ATDC5 cells, IL-1β decreases the levels of aggrecan and type II collagen but significantly increased the metalloproteinase-13 (Mmp13) mRNA by real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis. An RAR inverse agonist (AGN194310) inhibited IL-1β-stimulated Mmp13 and Ccn2 mRNA in a dose-dependent manner. Phosphorylated extracellular signal regulated-kinases (pERK1/2) and p-p38 mitogen-activated protein kinase (MAPK) were increased time-dependently by IL-1β treatment, and the IL-1β-induced p-p38 MAPK was inhibited by AGN194310. Experimental p38 inhibition led to a drop in the IL-1β-stimulated expressions of Mmp13 and Ccn2 mRNA. MMP13, CCN2, and p-p38 MAPK were expressed in hypertrophic chondrocytes near the invaded vascular endothelial cells. As a whole, these results point to role of the IL-1β via p38 MAPK as important signaling in the regulation of the endochondral bone formation in fracture healing, and to the actions of RAR inverse agonists as potentially relevant modulators of this process.

  30. Sonic Hedgehog Signaling and Tooth Development. International-journal Peer-reviewed

    Akihiro Hosoya, Nazmus Shalehin, Hiroaki Takebe, Tsuyoshi Shimo, Kazuharu Irie

    International journal of molecular sciences　21　(5)　2020/02/26

    DOI： 10.3390/ijms21051587 　

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    Sonic hedgehog (Shh) is a secreted protein with important roles in mammalian embryogenesis. During tooth development, Shh is primarily expressed in the dental epithelium, from initiation to the root formation stages. A number of studies have analyzed the function of Shh signaling at different stages of tooth development and have revealed that Shh signaling regulates the formation of various tooth components, including enamel, dentin, cementum, and other soft tissues. In addition, dental mesenchymal cells positive for Gli1, a downstream transcription factor of Shh signaling, have been found to have stem cell properties, including multipotency and the ability to self-renew. Indeed, Gli1-positive cells in mature teeth appear to contribute to the regeneration of dental pulp and periodontal tissues. In this review, we provide an overview of recent advances related to the role of Shh signaling in tooth development, as well as the contribution of this pathway to tooth homeostasis and regeneration.

  31. Sonic Hedgehog Regulates Bone Fracture Healing. International-journal Peer-reviewed

    Hiroaki Takebe, Nazmus Shalehin, Akihiro Hosoya, Tsuyoshi Shimo, Kazuharu Irie

    International journal of molecular sciences　21　(2)　2020/01/20

    DOI： 10.3390/ijms21020677 　

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    Bone fracture healing involves the combination of intramembranous and endochondral ossification. It is known that Indian hedgehog (Ihh) promotes chondrogenesis during fracture healing. Meanwhile, Sonic hedgehog (Shh), which is involved in ontogeny, has been reported to be involved in fracture healing, but the details had not been clarified. In this study, we demonstrated that Shh participated in fracture healing. Six-week-old Sprague-Dawley rats and Gli-CreERT2; tdTomato mice were used in this study. The right rib bones of experimental animals were fractured. The localization of Shh and Gli1 during fracture healing was examined. The localization of Gli1 progeny cells and osterix (Osx)-positive cells was similar during fracture healing. Runt-related transcription factor 2 (Runx2) and Osx, both of which are osteoblast markers, were observed on the surface of the new bone matrix and chondrocytes on day seven after fracture. Shh and Gli1 were co-localized with Runx2 and Osx. These findings suggest that Shh is involved in intramembranous and endochondral ossification during fracture healing.

  32. Odontoblast Cell Death Drives Stem Cell-Independent Cell-Rich Zone-Derived Dental Tissue Regeneration

    Lijuan Zhao, Atsushi Arai, Nobuyuki Udagawa, Kanji Horibe, Miroku Hara, Daisuke Nishida, Akihiro Hosoya, Rinya Masuko, Koji Okabe, Masashi Shin, Xianqi Li, Koichi Matsuo, Yasuhiro Kobayashi, Hideaki Kagami, Toshihide Mizoguchi

    SSRN Electronic Journal　2020

    Publisher: Elsevier BV

    DOI： 10.2139/ssrn.3696761 　

    eISSN： 1556-5068

  33. M2 Phenotype Macrophages Colocalize with Schwann Cells in Human Dental Pulp Peer-reviewed

    Journal of Dental Research　論文受理　(印刷中)　2019/11

  34. ケモカインCCL25が骨組織に与える影響

    高橋 拓実, 二宮 禎, 細矢 明宏, 中村 浩彰, 雪田 聡, 岩本 莉奈, 茶山 和敏

    Journal of Oral Biosciences Supplement　2019　114-114　2019/10

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  35. Gli1陽性歯根膜細胞は幹細胞特性を有し、歯槽骨再生に寄与する(Gli1-positive periodontal ligament cells possess stem cell properties and contribute to alveolar bone regeneration)

    Nazmus Shakehin, 細矢 明宏, 建部 廣明, 溝口 利英, 吉羽 永子, 吉羽 邦彦, 中村 浩彰, Hasan Md Riasat, 入江 一元

    Journal of Oral Biosciences Supplement　2019　231-231　2019/10

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  36. 象牙芽細胞の枯渇は象牙質形成を誘導する

    趙 麗娟, 荒井 敦, 宇田川 信之, 細矢 明宏, 岡部 幸司, 進 正史, 李 憲起, 小林 泰浩, 高橋 直之, 溝口 利英, 各務 秀明

    Journal of Oral Biosciences Supplement　2019　171-171　2019/10

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  37. ヒト歯髄においてシュワン細胞はマクロファージをM2型へ転換する

    吉羽 永子, 大倉 直人, 前川 知樹, 泉 健次, 細矢 明宏, 中村 浩彰, 前田 健康, 野杁 由一郎, 吉羽 邦彦, 枝並 直樹, 遠間 愛子

    Journal of Oral Biosciences Supplement　2019　302-302　2019/10

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  38. Detection of bone marrow-derived fibrocytes in human dental pulp repair. International-journal Peer-reviewed

    N Yoshiba, N Edanami, A Tohma, R Takeuchi, N Ohkura, A Hosoya, Y Noiri, H Nakamura, K Yoshiba

    International endodontic journal　51　(11)　1187-1195　2018/11

    DOI： 10.1111/iej.12940 　

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    AIM: To explore the expression profile of CD45+/pro-collagen I+ fibrocytes in intact dental pulps as well as during wound healing in adult dental pulp tissue. METHODOLOGY: A total of 16 healthy permanent teeth were obtained from young patients (18 to 25 years) undergoing orthodontic treatment. Routine pulp capping with mineral trioxide aggregate (MTA) was performed under local anaesthesia to induce a mineralized barrier at the exposed surface. Teeth were extracted from patients after 7, 14 and 35 days. Sections of the extracted teeth were prepared and stained for various markers using indirect immunofluorescence. Fibrocytes were counted, and the data were statistically evaluated using the Dunnett test. RESULTS: In uninflammed pulp tissue, a pro-collagen I-positive reaction was detected in odontoblasts, as well as in perivascular cells. Most of the CD45-positive cells were negative for pro-collagen I in normal pulp tissue, whereas CD45+/pro-collagen I+ fibrocytes were detected 7 days after injury. At day 14, fibrocytes were recognized under the fibrous matrix in contact with MTA and had infiltrated into regions of new capillary formation, where the fibrocytes were positively stained for vascular endothelial growth factor. By 35 days, fibrocytes were few, coincident with the formation of dentine bridges. The number of fibrocytes peaked 7 days post-injury and decreased at 14 days. CONCLUSIONS: The presence of fibrocytes in human pulp wound healing was observed. The spatiotemporal distribution of fibrocytes suggests that fibrocytes are involved in the early stages of pulp wound healing, specifically by contributing to new blood vessel formation.

  39. CCL25遺伝子欠損マウスの骨組織解析

    前田 久留実, 二宮 禎, 細矢 明宏, 中村 宏彰

    Journal of Oral Biosciences Supplement　2018　166-166　2018/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  40. 象牙芽細胞の枯渇は修復象牙質を誘導する

    趙 麗娟, 荒井 敦, 堀部 寛治, 楊 孟雨, 細矢 明宏, 小林 泰浩, 宇田川 信之, 高橋 直之, 溝口 利英, 李 憲起, 各務 秀明

    日本骨代謝学会学術集会プログラム抄録集　36回　177-177　2018/07

    Publisher: (一社)日本骨代謝学会

    ISSN： 1349-0761

  41. 副甲状腺ホルモン間欠投与とメカニカルストレスが歯槽骨に及ぼす影響 Peer-reviewed

    建部 廣明, Shalehin Nazmus, Hasan Md Riasat, 細矢 明宏, 入江 一元

    北海道医療大学歯学雑誌　37　(1)　17-24　2018/06

    Publisher: 北海道医療大学歯学会

    ISSN： 1880-5892

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    6週齢雄性SDラットを用い、吸入麻酔および全身麻酔を施し、上顎左側第一臼歯を抜去した。術後から、副甲状腺ホルモン(PTH:テリパラチド)を投与するP群、生理食塩水を投与するC群に分けた。実験4日、カテプシンK(CathK)とCD68陽性細胞数は、P群がC群に比べて有意に多かった。実験7日のP群では組織非特異的アルカリホスファターゼ(TNALP)陽性を示す細胞層が厚く、形態計測によっても有意差を認めた。Osterix陽性細胞は、骨表面から骨髄側に向かって広い範囲に局在を認め、Osterix陽性細胞数もP群がC群に比べ有意に多かった。P群では、非抜歯側が抜歯側と比較してTNALP陽性細胞層が厚く、Osterix陽性細胞数が多い傾向を示した。実験28日、P群はC群に比べて骨梁が有意に太かった。P群では、骨表面に沿って厚いTNALP陽性細胞層を認め、C群に比べTNALP陽性を示す細胞層が有意に厚かった。P群では非抜歯側が抜歯側に比較して歯槽骨面積が広く、TNALP陽性細胞層が厚い傾向を示した。

  42. Expression and localization of CRAMP in rat tooth germ and during reparative dentin formation Peer-reviewed

    Kanji Horibe, Akihiro Hosoya, Toru Hiraga, Hiroaki Nakamura

    Clinical Oral Investigations　22(7)　1-8　2018/02/02

    Publisher: Springer Verlag

    DOI： 10.1007/s00784-018-2353-x 　

    ISSN： 1436-3771 1432-6981

  43. Minodronic acid induces morphological changes in osteoclasts at bone resorption sites and reaches a level required for antagonism of purinergic P2X2/3 receptors Peer-reviewed

    Makoto Tanaka, Akihiro Hosoya, Hiroshi Mori, Ryoji Kayasuga, Hiroaki Nakamura, Hidehiro Ozawa

    Journal of Bone and Mineral Metabolism　36　(1)　54-63　2018/01/01

    Publisher: Springer Tokyo

    DOI： 10.1007/s00774-017-0814-y 　

    ISSN： 1435-5604 0914-8779

  44. Localization of RELM-beta/FIZZ2 Is Associated with Cementum Formation Peer-reviewed

    Akihiro Hosoya, Akira Takahama, Hiroaki Nakamura

    ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY　300　(10)　1865-1874　2017/10

    DOI： 10.1002/ar.23636 　

    ISSN： 1932-8486

    eISSN： 1932-8494

  45. ケモカインCCL25投与が乳幼児期マウス骨形成に与える影響

    雪田 聡, 二宮 禎, 細矢 明宏, 中村 浩彰, 茶山 和敏, 夏目 真帆, 前田 久留実, 佐野 隆之

    Journal of Oral Biosciences Supplement　2017　244-244　2017/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  46. VDR in Osteoblast-Lineage Cells Primarily Mediates Vitamin D Treatment-Induced Increase in Bone Mass by Suppressing Bone Resorption. International-journal Peer-reviewed

    Yuko Nakamichi, Nobuyuki Udagawa, Kanji Horibe, Toshihide Mizoguchi, Yoko Yamamoto, Takashi Nakamura, Akihiro Hosoya, Shigeaki Kato, Tatsuo Suda, Naoyuki Takahashi

    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research　32　(6)　1297-1308　2017/06

    DOI： 10.1002/jbmr.3096 　

    ISSN： 0884-0431

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    Long-term treatment with active vitamin D [1α,25(OH)2 D3 ] and its derivatives is effective for increasing bone mass in patients with primary and secondary osteoporosis. Derivatives of 1α,25(OH)2 D3 , including eldecalcitol (ELD), exert their actions through the vitamin D receptor (VDR). ELD is more resistant to metabolic degradation than 1α,25(OH)2 D3 . It is reported that ELD treatment causes a net increase in bone mass by suppressing bone resorption rather than by increasing bone formation in animals and humans. VDR in bone and extraskeletal tissues regulates bone mass and secretion of osteotropic hormones. Therefore, it is unclear what types of cells expressing VDR preferentially regulate the vitamin D-induced increase in bone mass. Here, we examined the effects of 4-week treatment with ELD (50 ng/kg/day) on bone using osteoblast lineage-specific VDR conditional knockout (Ob-VDR-cKO) and osteoclast-specific VDR cKO (Ocl-VDR-cKO) male mice aged 10 weeks. Immunohistochemically, VDR in bone was detected preferentially in osteoblasts and osteocytes. Ob-VDR-cKO mice showed normal bone phenotypes, despite no appreciable immunostaining of VDR in bone. Ob-VDR-cKO mice failed to increase bone mass in response to ELD treatment. Ocl-VDR-cKO mice also exhibited normal bone phenotypes, but normally responded to ELD. ELD-induced FGF23 production in bone was regulated by VDR in osteoblast-lineage cells. These findings suggest that the vitamin D treatment-induced increase in bone mass is mediated by suppressing bone resorption through VDR in osteoblast-lineage cells. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

  47. Relationship between localization of proteoglycans and induction of neurotrophic factors in mouse dental pulp Peer-reviewed

    Akira Yukita, Miroku Hara, Akihiro Hosoya, Hiroaki Nakamura

    Journal of Oral Biosciences　59　(1)　31-37　2017/02/01

    Publisher: Japanese Association for Oral Biology

    DOI： 10.1016/j.job.2016.10.001 　

    ISSN： 1349-0079

  48. Induced differentiation of rat periodontal ligament-derived cells using growth factor cocktail Peer-reviewed

    Michiko Nakatsuka, 細矢 明宏, Koichiro Jin, Ji-Youn Kim, Satoshi Fujita, Hironori Akiyama, Shoko Gamoh, Shunji Kumabe

    J Dent Oral Health　3(9)　96　2017

  49. Vitamin D treatment increases bone mass through VDR in osteoblast-lineage cells Peer-reviewed

    Yuko Nakamichi, Nobuyuki Udagawa, Kanji Horibe, Toshihide Mizoguchi, Yoko Yamamoto, Takashi Nakamura, 細矢 明宏, Shigeaki Kato, Tatsuo Suda, Naoyuki Takahashi

    J Bone Miner Res　32(6)　1297-1308　2017

  50. 象牙芽細胞分化におけるポリコーム群タンパク質Bmi1の機能

    細矢 明宏, 吉羽 邦彦, 吉羽 永子, 鷲尾 絢子, 諸冨 孝彦, 北村 知昭, 山本 昭夫, 中村 浩彰

    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　43-43　2016/10

    Publisher: (NPO)日本歯科保存学会

  51. 抜歯痕修復における間葉系幹細胞のCD91の機能的役割

    二宮 禎, 細矢 明宏, 中村 浩彰

    Journal of Oral Biosciences Supplement　2016　347-347　2016/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  52. スフェロイド形成による骨髄由来間葉系幹細胞の軟骨細胞への分化誘導

    中塚 美智子, 細矢 明宏, 隈部 俊二, 田村 功

    Journal of Oral Biosciences Supplement　2016　472-472　2016/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  53. 骨髄間葉系細胞におけるCD91の機能的役割

    二宮 禎, 細矢 明宏

    日本骨代謝学会学術集会プログラム抄録集　34回　225-225　2016/07

    Publisher: (一社)日本骨代謝学会

    ISSN： 1349-0761

  54. ビタミンDの骨量増加の薬理作用は、破骨細胞ではなく骨芽細胞のVDRを介する

    中道 裕子, 溝口 利英, 山本 陽子, 中村 貴, 細矢 明宏, 堀部 寛治, 原田 卓, 斎藤 一史, 加藤 茂明, 須田 立雄, 宇田川 信之, 高橋 直之

    日本骨代謝学会学術集会プログラム抄録集　34回　181-181　2016/07

    Publisher: (一社)日本骨代謝学会

    ISSN： 1349-0761

  55. GaAlAs laser-induced pulp mineralization involves dentin matrix protein 1 and osteopontin expression Peer-reviewed

    Y. Shigetani, N. Ohkura, K. Yoshiba, H. Ohshima, A. Hosoya, N. Yoshiba, T. Okiji

    ORAL DISEASES　22　(5)　399-405　2016/07

    DOI： 10.1111/odi.12461 　

    ISSN： 1354-523X

    eISSN： 1601-0825

  56. 骨髄由来間葉系幹細胞の軟骨細胞への分化誘導

    中塚 美智子, 松田 哲史, 細矢 明宏, 隈部 俊二

    Journal of Oral Biosciences Supplement　2015　403-403　2015/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  57. 歯根膜由来細胞の分化誘導に有用な成長因子の検討

    中塚 美智子, 隈部 俊二, 細矢 明宏, 上田 甲寅, 松田 哲史, 岩井 康智

    日本口腔科学会雑誌　64　(2)　213-214　2015/07

    Publisher: (NPO)日本口腔科学会

    ISSN： 0029-0297

  58. Correlation between Fibrillin-1 Degradation and mRNA Downregulation and Myofibroblast Differentiation in Cultured Human Dental Pulp Tissue Peer-reviewed

    Nagako Yoshiba, Kunihiko Yoshiba, Naoto Ohkura, Erika Takei, Naoki Edanami, Youhei Oda, Akihiro Hosoya, Hiroaki Nakamura, Takashi Okiji

    JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY　63　(6)　438-448　2015/06

    DOI： 10.1369/0022155415580622 　

    ISSN： 0022-1554

    eISSN： 1551-5044

  59. Ability of stem and progenitor cells in the dental pulp to form hard tissue Peer-reviewed

    Akihiro Hosoya, Hiroaki Nakamura

    Japanese Dental Science Review　51　(3)　75-83　2015

    Publisher: Elsevier Ltd

    DOI： 10.1016/j.jdsr.2015.03.002 　

    ISSN： 2213-6851 1882-7616

  60. 象牙芽細胞分化におけるBmi-1の機能

    細矢 明宏, 二宮 禎, 吉羽 邦彦, 吉羽 永子, 中塚 美智子, 中村 浩彰

    Journal of Oral Biosciences Supplement　2014　184-184　2014/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  61. 成長因子カクテルを用いた歯根膜由来細胞の分化誘導実験

    隈部 俊二, 中塚 美智子, 細矢 明宏, 上田 甲寅, 乾 千珠子, 森下 愛子, 岩井 康智

    Journal of Oral Biosciences Supplement　2014　193-193　2014/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  62. Enhanced Bone-Forming Activity of Side Population Cells in the Periodontal Ligament Peer-reviewed

    Tadashi Ninomiya, Toru Hiraga, Akihiro Hosoya, Kiyoshi Ohnuma, Yuzuru Ito, Masafumi Takahashi, Susumu Ito, Makoto Asashima, Hiroaki Nakamura

    CELL TRANSPLANTATION　23　(6)　691-701　2014

    DOI： 10.3727/096368913X663587 　

    ISSN： 0963-6897

    eISSN： 1555-3892

  63. Localization of SUMOylation factors and Osterix in odontoblast lineage cells during dentin formation and regeneration Peer-reviewed

    Akihiro Hosoya, Akira Yukita, Tadashi Ninomiya, Toru Hiraga, Kunihiko Yoshiba, Nagako Yoshiba, Etsuo Kasahara, Hiroaki Nakamura

    HISTOCHEMISTRY AND CELL BIOLOGY　140　(2)　201-211　2013/08

    DOI： 10.1007/s00418-013-1076-y 　

    ISSN： 0948-6143

  64. ヒト歯髄創傷治癒過程における細胞外基質の局在変化—Fibrillin-1基質の動的リモデリングに関する検索— Peer-reviewed

    吉羽永子, 吉羽邦彦, 大倉直人, 重谷佳見, 武井絵梨花, 細矢明宏, 中村浩彰, 興地隆史

    日歯保誌　56(3)　(3)　161-168　2013

    Publisher: (NPO)日本歯科保存学会

    DOI： 10.11471/shikahozon.56.161 　

    ISSN： 0387-2343

    eISSN： 2188-0808

  65. コラーゲンゲルを用いたヒト間葉系幹細胞HMS0014の分化誘導実験

    中塚 美智子, 隈部 俊二, 橋本 典也, 細矢 明宏, 岩井 康智

    日本再生歯科医学会誌　10　(1)　42-42　2012/12

    Publisher: 日本再生歯科医学会

    ISSN： 1348-9615

    eISSN： 1880-0815

  66. Two Distinct Processes of Bone-like Tissue Formation by Dental Pulp Cells after Tooth Transplantation Peer-reviewed

    Akihiro Hosoya, Akira Yukita, Kunihiko Yoshiba, Nagako Yoshiba, Masafumi Takahashi, Hiroaki Nakamura

    JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY　60　(11)　861-873　2012/11

    DOI： 10.1369/0022155412459741 　

    ISSN： 0022-1554

  67. Immunohistochemical analysis of two stem cell markers of alpha-smooth muscle actin and STRO-1 during wound healing of human dental pulp Peer-reviewed

    Nagako Yoshiba, Kunihiko Yoshiba, Naoto Ohkura, Yoshimi Shigetani, Erika Takei, Akihiro Hosoya, Hiroaki Nakamura, Takashi Okiji

    HISTOCHEMISTRY AND CELL BIOLOGY　138　(4)　583-592　2012/10

    DOI： 10.1007/s00418-012-0978-4 　

    ISSN： 0948-6143

  68. コラーゲンゲルにおけるHMS0014間葉系幹細胞の三次元培養による硬組織形成能の評価

    中塚 美智子, 隈部 俊二, 細矢 明宏, 安 春英, 上田 甲寅, 乾 千珠子, 松田 哲史, 岩井 康智

    Journal of Oral Biosciences Supplement　2012　167-167　2012/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  69. Thy-1-positive cells in the subodontoblastic layer possess high potential to differentiate into hard tissue-forming cells Peer-reviewed

    Akihiro Hosoya, Toru Hiraga, Tadashi Ninomiya, Akira Yukita, Kunihiko Yoshiba, Nagako Yoshiba, Masafumi Takahashi, Susumu Ito, Hiroaki Nakamura

    HISTOCHEMISTRY AND CELL BIOLOGY　137　(6)　733-742　2012/06

    DOI： 10.1007/s00418-012-0928-1 　

    ISSN： 0948-6143

  70. Ubc9 negatively regulates BMP-mediated osteoblastic differentiation in cultured cells Peer-reviewed

    Akira Yukita, Akihiro Hosoya, Yuzuru Ito, Takenobu Katagiri, Makoto Asashima, Hiroaki Nakamura

    BONE　50　(5)　1092-1099　2012/05

    DOI： 10.1016/j.bone.2012.02.008 　

    ISSN： 8756-3282

  71. 1 alpha,25-Dihydroxyvitamin D3 inhibits osteoblastic differentiation of mouse periodontal fibroblasts Peer-reviewed

    Yen-Chen Chen, Tadashi Ninomiya, Akihiro Hosoya, Toru Hiraga, Hiroo Miyazawa, Hiroaki Nakamura

    ARCHIVES OF ORAL BIOLOGY　57　(5)　453-459　2012/05

    DOI： 10.1016/j.archoralbio.2011.10.005 　

    ISSN： 0003-9969

  72. The molecular chaperone Hsp47 is essential for cartilage and endochondral bone formation Peer-reviewed

    Yusaku Masago, Akihiro Hosoya, Kunito Kawasaki, Shogo Kawano, Akira Nasu, Junya Toguchida, Katsumasa Fujita, Hiroaki Nakamura, Gen Kondoh, Kazuhiro Nagata

    JOURNAL OF CELL SCIENCE　125　(5)　1118-1128　2012/03

    DOI： 10.1242/jcs.089748 　

    ISSN： 0021-9533

  73. Expressional Alterations of Fibrillin-1 during Wound Healing of Human Dental Pulp Peer-reviewed

    Nagako Yoshiba, Kunihiko Yoshiba, Naoto Ohkura, Akihiro Hosoya, Yoshimi Shigetani, Yusuke Yamanaka, Naoya Izumi, Hiroaki Nakamura, Takashi Okiji

    JOURNAL OF ENDODONTICS　38　(2)　177-184　2012/02

    DOI： 10.1016/j.joen.2011.09.016 　

    ISSN： 0099-2399

  74. Role of heparan sulfate proteoglycans surrounding osteoblast lineage cells Peer-reviewed

    Hiroaki Nakamura, Akira Yukita, Tadashi Ninomiya, Akihiro Hosoya, Toru Hiraga

    Journal of Oral Biosciences　54　(1)　43-47　2012

    Publisher: Japanese Association for Oral Biology

    DOI： 10.1016/j.job.2012.01.005 　

    ISSN： 1349-0079

  75. ヒト間葉系幹細胞を用いた歯科用インプラント体表面への細胞接着実験

    隈部 俊二, 中塚 美智子, 橋本 典也, 安 春英, 上田 甲寅, 三上 豊, 細矢 明宏, 黄 宏智, 岩井 康智

    日本再生歯科医学会誌　9　(1)　62-62　2011/12

    Publisher: 日本再生歯科医学会

    ISSN： 1348-9615

    eISSN： 1880-0815

  76. ヒト間葉系幹細胞を用いた硬組織形成実験

    中塚 美智子, 隈部 俊二, 橋本 典也, 乾 千珠子, 岸本 直隆, 細矢 明宏, 松田 哲史, 森下 愛子, 岩井 康智

    日本再生歯科医学会誌　9　(1)　69-69　2011/12

    Publisher: 日本再生歯科医学会

    ISSN： 1348-9615

    eISSN： 1880-0815

  77. Runx3 is a crucial regulator of alveolar differentiation and lung tumorigenesis in mice Peer-reviewed

    Jong-Min Lee, Jeong-Oh Shin, Kyoung-Won Cho, Akihiro Hosoya, Sung-Won Cho, You-Soub Lee, Hyun-Mo Ryoo, Suk-Chul Bae, Han-Sung Jung

    DIFFERENTIATION　81　(4)　261-268　2011/04

    DOI： 10.1016/j.diff.2011.02.001 　

    ISSN： 0301-4681

  78. Prostaglandin E-2 receptor EP4-selective agonist (ONO-4819) increases bone formation by modulating mesenchymal cell differentiation Peer-reviewed

    Tadashi Ninomiya, Akihiro Hosoya, Toru Hiraga, Masanori Koide, Kojiro Yamaguchi, Hiroji Oida, Yoshinori Arai, Noriyuki Sahara, Hiroaki Nakamura, Hidehiro Ozawa

    EUROPEAN JOURNAL OF PHARMACOLOGY　650　(1)　396-402　2011/01

    DOI： 10.1016/j.ejphar.2010.10.021 　

    ISSN： 0014-2999

  79. Temporomandibular joint response to mandibular deviation in rabbits detected by 3D micro-CT imaging Peer-reviewed

    Chen Zhao, Hiroshi Kurita, Kenji Kurashina, Akihiro Hosoya, Yoshinori Arai, Hiroaki Nakamura

    ARCHIVES OF ORAL BIOLOGY　55　(12)　929-937　2010/12

    DOI： 10.1016/j.archoralbio.2010.07.019 　

    ISSN： 0003-9969

  80. Immunohistochemical Localization of Cytokeratins in the Junctional Region of Ectoderm and Endoderm Peer-reviewed

    Akihiro Hosoya, Sungwook Kwak, Eun-Jung Kim, Declan Patrick Lunny, E. Birgitte Lane, Sung-Won Cho, Han-Sung Jung

    ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY　293　(11)　1864-1872　2010/11

    DOI： 10.1002/ar.21233 　

    ISSN： 1932-8486

  81. Administration of the Bisphosphonate Zoledronic Acid During Tooth Development Inhibits Tooth Eruption and Formation and Induces Dental Abnormalities in Rats Peer-reviewed

    Toru Hiraga, Tadashi Ninomiya, Akihiro Hosoya, Hiroaki Nakamura

    CALCIFIED TISSUE INTERNATIONAL　86　(6)　502-510　2010/06

    DOI： 10.1007/s00223-010-9366-z 　

    ISSN： 0171-967X

  82. Runx3 is required for the differentiation of lung epithelial cells and suppression of lung cancer Peer-reviewed

    K-S Lee, Y-S Lee, J-M Lee, K. Ito, S. Cinghu, J-H Kim, J-W Jang, Y-H Li, Y-M Goh, X-Z Chi, H. Wee, H-W Lee, A. Hosoya, J-H Chung, J-J Jang, J. K. Kundu, Y-J Surh, W-J Kim, Y. Ito, H-S Jung, S-C Bae

    ONCOGENE　29　(23)　3349-3361　2010/06

    DOI： 10.1038/onc.2010.79 　

    ISSN： 0950-9232

  83. Localization of Thy-1-positive Cells in the Perichondrium During Endochondral Ossification Peer-reviewed

    Hiroaki Nakamura, Akira Yukita, Tadashi Ninomiya, Akihiro Hosoya, Toru Hiraga, Hidehiro Ozawa

    JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY　58　(5)　455-462　2010/05

    DOI： 10.1369/jhc.2010.955393 　

    ISSN： 0022-1554

  84. Potential of periodontal ligament cells to regenerate alveolar bone Peer-reviewed

    Akihiro Hosoya, Tadashi Ninomiya, Toru Hiraga, Kunihiko Yoshiba, Nagako Yoshiba, Etsuo Kasahara, Hidehiro Ozawa, Hiroaki Nakamura

    Journal of Oral Biosciences　52　(2)　72-80　2010

    Publisher: Japanese Association for Oral Biology

    DOI： 10.2330/joralbiosci.52.72 　

    ISSN： 1349-0079

  85. ERK Activation is Involved in Tooth Development via FGF10 Signaling Peer-reviewed

    Kyoung-Won Cho, Jinglei Cai, Hyun-Yi Kim, Akihiro Hosoya, Hayato Ohshima, Kang-Yell Choi, Han-Sung Jung

    JOURNAL OF EXPERIMENTAL ZOOLOGY PART B-MOLECULAR AND DEVELOPMENTAL EVOLUTION　312B　(8)　901-911　2009/12

    DOI： 10.1002/jez.b.21309 　

    ISSN： 1552-5007

  86. Chick Tooth Induction Revisited Peer-reviewed

    Jinglei Cai, Sung-Won Cho, Mikio Ishiyama, Masato Mikami, Akihiro Hosoya, Yukishige Kozawa, Hayato Ohshima, Han-Sung Jung

    JOURNAL OF EXPERIMENTAL ZOOLOGY PART B-MOLECULAR AND DEVELOPMENTAL EVOLUTION　312B　(5)　465-472　2009/07

    DOI： 10.1002/jez.b.21265 　

    ISSN： 1552-5007

  87. Formation of bone-like mineralized matrix by periodontal ligament cells in vivo: a morphological study in rats Peer-reviewed

    Toru Hiraga, Tadashi Ninomiya, Akihiro Hosoya, Masafumi Takahashi, Hiroaki Nakamura

    JOURNAL OF BONE AND MINERAL METABOLISM　27　(2)　149-157　2009/03

    DOI： 10.1007/s00774-009-0039-9 　

    ISSN： 0914-8779

  88. Identification of cell cycle-arrested quiescent osteoclast precursors in vivo.

    Mizoguchi Toshihide, Muto Akinori, Udagawa Nobuyuki, Arai Atsushi, Yamashita Teruhito, Hosoya Akihiro, Ninomiya Tadashi, Nakamura Hiroaki, Yamamoto Yohei, Kinugawa Saya, Nakamura Midori, Nakamichi Yuko, Kobayashi Yasuhiro, Nagasawa Sakae, Oda Kimimitsu, Tanaka Hirofumi, Tagaya Mitsuo, Penninger Josef M, Ito Michio, Takahashi Naoyuki

    J Cell Biol　184　(4)　541-554　2009/02/23

    DOI： 10.1083/jcb.200806139 　

    ISSN： 1540-8140

    More details Close

    Osteoclasts are multinucleated cells that resorb bone. Although osteoclasts originate from the monocyte/macrophage lineage, osteoclast precursors are not well characterized in vivo. The relationship between proliferation and differentiation of osteoclast precursors is examined in this study using murine macrophage cultures treated with macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-kappaB (RANK) ligand (RANKL). Cell cycle-arrested quiescent osteoclast precursors (QuOPs) were identified as the committed osteoclast precursors in vitro. In vivo experiments show that QuOPs survive for several weeks and differentiate into osteoclasts in response to M-CSF and RANKL. Administration of 5-fluorouracil to mice induces myelosuppression, but QuOPs survive and differentiate into osteoclasts in response to an active vitamin D(3) analogue given to those mice. Mononuclear cells expressing c-Fms and RANK but not Ki67 are detected along bone surfaces in the vicinity of osteoblasts in RANKL-deficient mice. These results suggest that QuOPs preexist at the site of osteoclastogenesis and that osteoblasts are important for maintenance of QuOPs.

  89. Identification of cell cycle-arrested quiescent osteoclast precursors in vivo Peer-reviewed

    Toshihide Mizoguchi, Akinori Muto, Nobuyuki Udagawa, Atsushi Arai, Teruhito Yamashita, Akihiro Hosoya, Tadashi Ninomiya, Hiroaki Nakamura, Yohei Yamamoto, Saya Kinugawa, Midori Nakamura, Yuko Nakamichi, Yasuhiro Kobayashi, Sakae Nagasawa, Kimimitsu Oda, Hirofumi Tanaka, Mitsuo Tagaya, Josef M. Penninger, Michio Ito, Naoyuki Takahashi

    JOURNAL OF CELL BIOLOGY　184　(4)　541-554　2009/02

    DOI： 10.1083/jcb.200806139 　

    ISSN： 0021-9525

  90. Expression of p63 during early craniofacial development of the mouse embryo Peer-reviewed

    細矢 明宏, Jong-Min Lee, Ji-Youn Kim, Han-Sung Jung, Sung-Won Cho

    Dev Reprod　13　(2)　89-95　2009

  91. Morphological evidence of basal keratinocyte migration during the re-epithelialization process Peer-reviewed

    Akihiro Hosoya, Jong-Min Lee, Sung-Won Cho, Ji-Youn Kim, Naoshi Shinozaki, Takahiko Shibahara, Masaki Shimono, Han-Sung Jung

    HISTOCHEMISTRY AND CELL BIOLOGY　130　(6)　1165-1175　2008/12

    DOI： 10.1007/s00418-008-0499-3 　

    ISSN： 0948-6143

  92. Involvement of cell-cell and cell-matrix interactions in bone destruction induced by metastatic MDA-MB-231 human breast cancer cells in nude mice Peer-reviewed

    Hiroaki Nakamura, Toru Hiraga, Tadashi Ninomiya, Akihiro Hosoya, Noboru Fujisaki, Toshiyuki Yoneda, Hidehiro Ozawa

    JOURNAL OF BONE AND MINERAL METABOLISM　26　(6)　642-647　2008/11

    DOI： 10.1007/s00774-008-0857-1 　

    ISSN： 0914-8779

    eISSN： 1435-5604

  93. BMP4 signaling regulates formation of Hertwig's epithelial root sheath during tooth root development Peer-reviewed

    Akihiro Hosoya, Ji-Youn Kim, Sung-Won Cho, Han-Sung Jung

    CELL AND TISSUE RESEARCH　333　(3)　503-509　2008/09

    DOI： 10.1007/s00441-008-0655-z 　

    ISSN： 0302-766X

  94. Alveolar bone regeneration of subcutaneously transplanted rat molar Peer-reviewed

    Akihiro Hosoya, Tadashi Ninomiya, Toru Hiraga, Chen Zhao, Kunihiko Yoshiba, Nagako Yoshiba, Masafumi Takahashi, Takahiro Okabe, Shigeyuki Wakitani, Hirohito Yamada, Etsuo Kasahara, Hidehiro Ozawa, Hiroaki Nakamura

    BONE　42　(2)　350-357　2008/02

    DOI： 10.1016/j.bone.2007.09.054 　

    ISSN： 8756-3282

  95. The role of BMP4 in HERS during tooth root development Peer-reviewed

    Han-Sung Jung, Akihiro Hosoya, Ji-Youn Kim, Sung-Won Cho

    Journal of Oral Biosciences　50　(3)　160-166　2008

    Publisher: Japanese Association for Oral Biology

    DOI： 10.2330/joralbiosci.50.160 　

    ISSN： 1349-0079

  96. 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

  97. 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

  98. Immunohistochemical study of hard tissue formation in the rat pulp cavity after tooth replantation Peer-reviewed

    Chen Zhao, Akihiro Hosoya, Hiroshi Kurita, Tao Hu, Toru Hiraga, Tadashi Ninomiya, Kunihiko Yoshiba, Nagako Yoshiba, Masafumi Takahashi, Kenji Kurashina, Hidehiro Ozawa, Hiroaki Nakamura

    ARCHIVES OF ORAL BIOLOGY　52　(10)　945-953　2007/10

    DOI： 10.1016/j.archoralbio.2007.04.015 　

    ISSN： 0003-9969

  99. Case of bone Paget&apos;s disease with cheek pain, hearing loss and tremor whose histological findings showed peculiar calcified structures Peer-reviewed

    Hiroyuki Kinoshita, Hirohiko Hirano, Akihiko Hosoya, Tadashi Ninomiya, Hidehiro Ozawa, Motoji Sawabe, Yasuyoshi Ouchi, Masatsune Yamaguchi, Takayuki Hosoi

    GERIATRICS & GERONTOLOGY INTERNATIONAL　7　(2)　189-194　2007/06

    DOI： 10.4111/j.1447-0594.2007.00393.x 　

    ISSN： 1444-1586

  100. Ripply2 is essential for precise somite formation during mouse early development Peer-reviewed

    Techuan Cha, Akiko Kondow, Akihiro Hosoya, Keisuke Hitachi, Akira Yukita, Koji Okabayashi, Hiroaki Nakamura, Hidehiro Ozawa, Hiroshi Kiyonari, Tatsuo Michiue, Yuzuru Ito, Makoto Asashima

    FEBS LETTERS　581　(14)　2691-2696　2007/06

    DOI： 10.1016/j.febslet.2007.05.017 　

    ISSN： 0014-5793

    eISSN： 1873-3468

  101. Hard tissue formation in subcutaneously transplanted rat dental pulp Peer-reviewed

    A. Hosoya, H. Nakamura, T. Ninomiya, K. Hoshi, K. Yoshiba, N. Yoshiba, M. Takahashi, T. Okabe, N. Sahara, H. Yamada, E. Kasahara, H. Ozawa

    JOURNAL OF DENTAL RESEARCH　86　(5)　469-474　2007/05

    DOI： 10.1177/154405910708600515 　

    ISSN： 0022-0345

  102. Application of Ozony Tron^【○!R】 to Endodontic Therapy : Antimicrobial Effects of Ozone Gas during Infected Root Canal Treatment Peer-reviewed

    YAMADA Hirohito, UCHIYAMA Makiko, HOSOYA Akihiro, NAKAMURA Hiroaki, YAMAMOTO Akio, KASAHARA Etsuo

    Jpn J Conserv Dent　50　(6)　657-663　2007

    Publisher: The Japanese Society of Conservative Dentistry

    DOI： 10.11471/shikahozon.50.657 　

    ISSN： 0387-2343

    More details Close

    In addition to the antimicrobial action produced by the oxidizing action of ozone, the tissue activation action of ozone can be applied in dentistry, with focus placed on its effectiveness as an antimicrobial, anti-inflammatory and hemostatic agent. We investigated the potential for using ozone water in the cleaning and disinfecting of artificial teeth and periodontal pockets, and as a cleaning fluid for root canal treatment. Recently, the Ozony Tron^[○!R], an ozone generator which produces ozone from available oxygen, was developed. This device does not require an oxygen tank to produce ozone, it has good portability due to its small size and weight, and it safely degrades the ozone gas released into oxygen, making it well suited for use during house calls. In this study we evaluated the clinical application of ozone gas treatment for infected root canals. From 155 devitalized teeth, where a positive culture was obtained in the root canal culture prior to enlargement of the root canal, there were 250 root canal samples on which the authors performed a routine root canal treatment following the enlargement standard (Yasuda's guidelines standard). After enlargement and preparation, 130 root canal samples were confirmed to have positive cultures, and these were the sample teeth used for this investigation. The sample teeth were randomly selected, and 88 root canals received ozone gas treatment and the remaining 42 root canals were irrigated alternately with Neo Cleaner and 3% oxydol and used as control teeth. Aerobic cultures were taken immediately following treatment, and a second culture test was taken during the patient's next visit before starting treatment, and these results were used to produce our findings. Moreover, we also used X-rays taken prior to surgery to investigate whether there was a correlation between presence of root lesions and ratio of positive cultures obtained. Results obtained were as follows. 1. Of the 250 root canals, we obtained a positive culture solely in root canal enlargement in 120 (48.0%). 2. Among the 88 cases where ozone gas was used, 42 root canals (47.7%) indicated no microbes, and of these, 10 root canals (11.4% of all cases) continued to have a negative culture into the second test. 3. In the cases with alternate irrigating, of the 42 root canals, 36 (85.7%) showed no microbes, and of these, 21 root canals (50.0% of all cases) continued to have a negative culture into the second test. 4. The correlation between radiolucent findings of the root and the ratio of positive cultures obtained indicated that, regardless of the presence of root lesions, the positive culture ratio for cases where ozone gas was used remained at approximately 50%. In cases where alternating irrigation was used, the positive culture ratio for root lesions (-) was 100%, (±) was 91.0%, and (+) was 64.0%.

  103. Increase of bone volume by a nanosecond pulsed laser irradiation is caused by a decreased osteoclast number and an activated osteoblasts Peer-reviewed

    Tadashi Ninomiya, Akihiro Hosoya, Hiroaki Nakamura, Kazuo Sano, Tsuyoshi Nishisaka, Hidehiro Ozawa

    BONE　40　(1)　140-148　2007/01

    DOI： 10.1016/j.bone.2006.07.026 　

    ISSN： 8756-3282

    eISSN： 1873-2763

  104. 破骨細胞前駆細胞はどのようにして骨組織に出現するか?

    中道 裕子, 溝口 利英, 武藤 昭紀, 宇田川 信之, 小林 泰浩, 細矢 明宏, 中村 美どり, 小澤 英浩, 高橋 直之

    松本歯学　32　(3)　264-265　2006/12

    Publisher: 松本歯科大学学会

    ISSN： 0385-1613

    eISSN： 2188-7233

  105. Immunohistochemical localization of alpha-smooth muscle actin during rat molar tooth development Peer-reviewed

    Akihiro Hosoya, Hiroaki Nakamura, Tadashi Ninomiya, Kunihiko Yoshiba, Nagako Yoshiba, Hiroyuki Nakaya, Shigeyuki Wakitani, Hirohito Yamada, Etsuo Kasahara, Hidehiro Ozawa

    JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY　54　(12)　1371-1378　2006/12

    DOI： 10.1369/jhc.6A6980.2006 　

    ISSN： 0022-1554

  106. 骨芽細胞はRANKL発現以外に破骨細胞形成のための微小環境を提供する

    山本 洋平, 中道 裕子, 堀内 博志, 中村 美どり, 細矢 明宏, 小澤 英浩, 伊藤 孝訓, 高岡 邦夫, 野口 俊英, 宇田川 信之, 高橋 直之

    日本骨代謝学会学術集会プログラム抄録集　24回　206-206　2006/07

    Publisher: (一社)日本骨代謝学会

    ISSN： 1349-0761

  107. Osteoblasts provide a suitable microenvironment for the action of receptor activator of nuclear factor-kappa B ligand Peer-reviewed

    Y Yamamoto, N Udagawa, S Matsuura, Y Nakamichi, H Horiuchi, A Hosoya, M Nakamura, H Ozawa, K Takaoka, JM Penninger, T Noguchi, N Takahashi

    ENDOCRINOLOGY　147　(7)　3366-3374　2006/07

    DOI： 10.1210/en.2006-0216 　

    ISSN： 0013-7227

  108. Scanning electron microscopy of the three different types of cementum in the molar teeth of the guinea pig Peer-reviewed

    K Moriyama, N Sahara, T Kageyama, Y Misawa, A Hosoya, H Ozawa

    ARCHIVES OF ORAL BIOLOGY　51　(6)　439-448　2006/06

    DOI： 10.1016/j.archoralbio.2005.07.001 　

    ISSN： 0003-9969

  109. Differential regulation of TIMP-1,-2, and-3 mRNA and protein expressions during mouse incisor development Peer-reviewed

    N Yoshiba, K Yoshiba, C Stoetzel, F Perrin-Schmitt, Y Cam, JV Ruch, A Hosoya, H Ozawa, H Lesot

    CELL AND TISSUE RESEARCH　324　(1)　97-104　2006/04

    DOI： 10.1007/s00441-005-0123-y 　

    ISSN： 0302-766X

  110. Effects of fixation and decalcification on the immunohistochemical localization of bone matrix proteins in fresh-frozen bone sections Peer-reviewed

    A Hosoya, K Hoshi, N Sahara, T Ninomiya, S Akahane, T Kawamoto, H Ozawa

    HISTOCHEMISTRY AND CELL BIOLOGY　123　(6)　639-646　2005/06

    DOI： 10.1007/s00418-005-0791-4 　

    ISSN： 0948-6143

  111. Immunohistochemical Study of Osteodentin in the Unerupted Rat Incisor Peer-reviewed

    Akihiro Hosoya, Hiroaki Nakamura, Shoji Akahane, Kunihiko Yoshiba, Nagako Yoshiba, Tadashi Ninomiya, Kazuto Hoshi, Noriyuki Sahara, Etsuo Kasahara, Hidehiro Ozawa

    journal of oral biosciences　48　(2)　132-137　2005

    DOI： 10.2330/joralbiosci.48.132 　

    ISSN： 1349-0079

  112. 加熱処理が球状ハイドロキシアパタイトの骨欠損部での骨伝導能に与える影響 Peer-reviewed

    渡邉敏之, 二宮 禎, 細矢明宏, 森山敬太, 佐原紀行, 小澤英浩, 溝口利英, 佐伯達哉, 伊藤充雄

    松本歯学　30(3)　228-237　2004

  113. Prostaglandin E EP4 receptor agonist induces the bone formation by an alteration of the osteoblast and osteoclast dynamic state Peer-reviewed

    Masaharu Tanaka, Noriyuki Sahara, Teruaki Katayama, Kojiro Yamaguchi, Akihiko Hosoya, Tadashi Ninomiya, Hidehiro Ozawa

    Journal of Toxicologic Pathology　17　(4)　253-260　2004

    DOI： 10.1293/tox.17.253 　

    ISSN： 0914-9198

  114. An immunohistochemical study on hard tissue formation in a subcutaneously transplanted rat molar Peer-reviewed

    A Hosoya, K Yoshiba, N Yoshiba, KT Hoshi, M Iwaku, H Ozawa

    HISTOCHEMISTRY AND CELL BIOLOGY　119　(1)　27-35　2003/01

    DOI： 10.1007/s00418-002-0478-z 　

    ISSN： 0948-6143

  115. Hard tissue formation in subcutaneously transplanted rat molars

    A Hosoya, K Yoshiba, N Yoshiba, M Iwaku, K Hoshi, H Ozawa

    DENTIN/PULP COMPLEX　166-167　2002

Show all ︎Show first 5

Misc. 75

  1. PTH投与によるGli1発現未分化間葉系細胞の細胞分化と骨組織内分布

    長谷川智香, 丸岡春日, 山本知真也, 山本知真也, 石津帆高, 石津帆高, 阿部未来, 原口(北構)真衣, 溝口利英, 細矢明宏, 網塚憲生

    日本骨形態計測学会雑誌　34　(1)　2024

    ISSN： 0917-4648

  2. メラノーマ骨微小環境におけるソニックヘッジホッグの役割

    平木 大地, Shamsoon Karnoon, 吉田 光希, 高畠 清文, 藤田 尚正, Nasrun Nisrina Ekayani, 長塚 仁, 安彦 善裕, 細矢 明宏, 志茂 剛

    日本口腔科学会雑誌　72　(2)　79-79　2023/07

    Publisher: (NPO)日本口腔科学会

    ISSN： 0029-0297

    eISSN： 2185-0461

  3. PTH投与後におけるGli1発現未分化間葉系細胞の骨組織内の細胞分化・分布について

    長谷川智香, 丸岡春日, 山本知真也, 山本知真也, 石津帆高, 石津帆高, 溝口利英, 細矢明宏, 網塚憲生

    日本骨代謝学会学術集会プログラム抄録集(CD-ROM)　41st　2023

    ISSN： 1349-0761

  4. Gli1陽性歯根膜細胞の抜歯窩治癒過程における動態解析

    藤井彩貴, 建部廣明, 志茂剛, 細矢明宏

    日本解剖学会総会・全国学術集会抄録集(CD-ROM)　127th　2022

  5. Three-dimensional morphological analysis of Dens invaginatus using micro CT

    Nazmus Shalehin

    39　(1)　11-15　2020/06

    Publisher: 北海道医療大学歯学会

    ISSN： 1880-5892

  6. ヒト歯髄においてシュワン細胞はマクロファージをM2型へ転換する

    吉羽永子, 大倉直人, 前川知樹, 泉健次, 細矢明宏, 中村浩彰, 前田健康, 野杁由一郎, 吉羽邦彦

    Journal of Oral Biosciences Supplement (Web)　2019　2019

    ISSN： 2187-9109

  7. ヒト歯髄組織創傷治癒過程における骨髄由来間葉系前駆細胞fibrocyteの動態検索

    吉羽 永子, 大倉 直人, 細矢 明宏, 中村 浩彰, 野杁 由一郎, 吉羽 邦彦, 枝並 直樹, 遠間 愛子, 竹内 亮介

    Journal of Oral Biosciences Supplement　2017　427-427　2017/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

  8. ヒト歯髄組織創傷治癒過程における骨髄由来間葉系前駆細胞fibrocyteの動態検索

    吉羽永子, 大倉直人, 細矢明宏, 中村浩彰, 野杁由一郎, 吉羽邦彦

    Journal of Oral Biosciences Supplement (Web)　2017　2017

    ISSN： 2187-9109

  9. 分泌タンパク質RELM-b/FIZZ2の歯根形成における役割

    細矢明宏, 建部廣明, 入江一元

    北医療誌　36(2)　47　2017

  10. 象牙芽細胞の分化と歯髄の硬組織形成能

    細矢明宏

    腎と骨代謝　29(1)　25-30　2016

    DOI： 10.19020/J02201.2016149815 　

  11. 歯根膜side population細胞の骨形成能

    二宮 禎, 細矢 明宏, 平賀 徹, 中村 浩彰

    THE BONE　28　(2)　113-117　2014/06

    Publisher: (株)メディカルレビュー社

    ISSN： 0914-7047

  12. iPS細胞から象牙芽細胞への分化誘導

    細矢明宏

    The BONE　28(3)　125　2014

  13. ヒト歯髄組織からoutgrowthする細胞による組織構築に関する研究

    吉羽 永子, 吉羽 邦彦, 大倉 直人, 細矢 明宏, 中村 浩彰, 興地 隆史

    Journal of Oral Biosciences Supplement　2013　193-193　2013/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

  14. ヒト歯髄組織からoutgrowthする細胞による組織構築に関する研究

    吉羽永子, 吉羽邦彦, 大倉直人, 細矢明宏, 中村浩彰, 興地隆史

    Journal of Oral Biosciences Supplement (Web)　2013　2013

    ISSN： 2187-9109

  15. An experiment on in vitro bone tissue formation by HMS0014 human mesenchymal cells cultured on surface modified titanium plates

    M. Nakatsuka, S. Kumabe, Y. Hashimoto, A. Hosoya, C. An, K. Ueda, C. Inui-Yamamoto, Y. Matsuda, Y. Mikami, Y. Iwai

    BONE　51　(6)　S17-S17　2012/12

    DOI： 10.1016/j.bone.2012.08.053 　

    ISSN： 8756-3282

  16. ラット炎症歯髄に対する薬物輸送担体の遺伝子発現解析

    大倉 直人, 重谷 佳見, 細矢 明宏, 吉羽 永子, 吉羽 邦彦, 興地 隆史

    Journal of Oral Biosciences Supplement　2012　160-160　2012/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

  17. ラット炎症歯髄に対する薬物輸送担体の遺伝子発現解析

    大倉 直人, 重谷 佳見, 細矢 明宏, 吉羽 永子, 吉羽 邦彦, 興地 隆史

    日本歯科医師会雑誌　65　(5)　628-628　2012/08

    Publisher: (公社)日本歯科医師会

    ISSN： 0047-1763

  18. 半導体レーザー照射後のラット臼歯における硬組織形成誘導機構の解明

    重谷 佳見, 大倉 直人, 細矢 明宏, 鈴木 啓展, 吉羽 邦彦, 吉羽 永子, 大島 勇人, 興地 隆史

    日本歯科医師会雑誌　65　(5)　629-629　2012/08

    Publisher: (公社)日本歯科医師会

    ISSN： 0047-1763

  19. ラット炎症歯髄に対する薬物輸送担体の遺伝子発現解析

    大倉直人, 重谷佳見, 細矢明宏, 吉羽永子, 吉羽邦彦, 興地隆史

    Journal of Oral Biosciences Supplement (Web)　2012　2012

    ISSN： 2187-9109

  20. ラクトフェリンの細胞分化調節機能

    二宮禎, 細矢明宏, 平賀徹, 小出雅則, 中村浩彰

    日本骨代謝学会学術集会プログラム抄録集　30th　243　2012

    ISSN： 1349-0761

  21. ラクトフェリンは細胞分化を制御し,卵巣摘出ラットの骨量減少を抑制する

    二宮禎, 細矢明宏, 平賀徹, 小出雅則, 中村浩彰

    Journal of Oral Biosciences Supplement (Web)　2012　ROMBUNNO.P2‐103 (WEB ONLY)　2012

    ISSN： 2187-9109

  22. ラット実験的炎症歯髄におけるプロスタノイド受容体遺伝子発現の経時的解析

    大倉 直人, 重谷 佳見, 細矢 明宏, 吉羽 永子, 吉羽 邦彦, 興地 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　134回　104-104　2011/05

    Publisher: (NPO)日本歯科保存学会

  23. ラット炎症歯髄に対する薬物輸送担体の遺伝子発現解析

    大倉 直人, 重谷 佳見, 細矢 明宏, 吉羽 永子, 吉羽 邦彦, 興地 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　133回　96-96　2010/10

    Publisher: (NPO)日本歯科保存学会

  24. 軟骨内骨化過程におけるThy-1(CD90)陽性細胞の役割

    中村 浩彰, 雪田 聡, 平賀 徹, 細矢 明宏, 二宮 禎, 小澤 英浩

    THE BONE　24　(3)　205-208　2010/08

    Publisher: (株)メディカルレビュー社

    ISSN： 0914-7047

  25. ヒト歯髄創傷治癒過程で生じるFibrillin-1の分解は細胞分化と石灰化を誘導する

    吉羽 永子, 吉羽 邦彦, 大倉 直人, 細矢 明宏, 重谷 佳見, 興地 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　132回　117-117　2010/05

    Publisher: (NPO)日本歯科保存学会

  26. 半導体レーザー照射後のラット臼歯における非コラーゲンタンパクの遺伝子発現

    重谷佳見, 大倉直人, 吉羽邦彦, 細矢明宏, 吉羽永子, 興地隆史

    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)　133rd　2010

  27. コラーゲン特異的分子シャペロンHSP47 は軟骨形成に重要である Peer-reviewed

    真砂有作, 細矢明宏, 河野章悟, 那須輝, 戸口田淳也, 藤田克昌, 小澤英浩, 近藤玄, 永田和宏

    京都大学再生医科学研究所学術講演会，京都市，2009.12.14　2009

  28. 歯髄を用いた再生療法の試み

    細矢明宏

    歯界展望　113(6)　1174-1175　2009

  29. Osteogenic Potential of Periodontal Ligament Cells in vivo

    T. Hiraga, T. Ninomiya, A. Hosoya, H. Nakamura

    JOURNAL OF BONE AND MINERAL RESEARCH　23　S255-S255　2008/09

    ISSN： 0884-0431

  30. 骨転移による骨破壊現象における細胞間、細胞基質間作用の重要性

    中村 浩彰, 平賀 徹, 細矢 明宏, 米田 俊之, 二宮 禎, 小澤 英浩

    THE BONE　22　(5)　575-579　2008/09

    Publisher: (株)メディカルレビュー社

    ISSN： 0914-7047

  31. Bone-like tissue formation in the pulp cavity after tooth replantation

    HOSOYA Akihiro, CHEN Zhao, YOSHIBA Kunihiko, YOSHIBA Nagako, YAMADA Hirohito, KASAHARA Etsuo, OZAWA Hidehiro, NAKAMURA Hiroaki

    51　88-88　2008/05/07

    ISSN： 0387-2343

  32. 歯根膜組織の歯槽骨再生能

    細矢明宏, 二宮 禎, 平賀 徹, Zhao Chen, 吉羽邦彦, 吉羽永子, 高橋将文, 岡部高弘, 脇谷滋之, 山田博仁, 笠原悦男, 小澤英浩, 中村浩彰

    The BONE　22(1)　3-7　2008

  33. 歯髄細胞の硬組織形成能について

    細矢 明宏, 平賀 徹, 中村 浩彰, Chen Zhao, 栗田 浩, 倉科 憲治, 二宮 禎, 小澤 英浩

    THE BONE　21　(6)　679-683　2007/11

    Publisher: (株)メディカルレビュー社

    ISSN： 0914-7047

  34. An osteoclast niche is composed of 5-FU-insensitive osteoclast precursors in vivo

    T. Mizoguchi, A. Muto, A. Hosoya, T. Yamashita, Y. Kobayashi, T. Ninomiya, Y. Nakamichi, N. Udagawa, M. Ito, N. Takahashi

    JOURNAL OF BONE AND MINERAL RESEARCH　22　S96-S96　2007/09

    ISSN： 0884-0431

  35. ラット歯髄皮下移植後の硬組織形成

    細矢 明宏, 中村 浩彰, 星 和人, 吉羽 邦彦, 吉羽 永子, 高橋 将文, 岡部 高弘, 山田 博仁, 笠原 悦男, 二宮 禎, 佐原 紀行, 小澤 英浩

    THE BONE　21　(4)　399-403　2007/07

    Publisher: (株)メディカルレビュー社

    ISSN： 0914-7047

  36. An immunohistochemical study on pulpal responses to mineral trioxide aggregate in human teeth

    YOSHIBA Kunihiko, YOSHIBA Nagako, SHIGETANI Yoshimi, HOSOYA Akihiro, OKIJI Takashi

    50　138-138　2007/05/07

    ISSN： 0387-2343

  37. 歯周組織発生過程におけるα-平滑筋アクチンの局在と歯槽骨形成との関連

    細矢明宏, 中村浩彰, 二宮 禎, 吉羽邦彦, 吉羽永子, 中谷宏幸, 脇谷滋之, 山田博仁, 笠原悦男, 小澤英浩

    The BONE　21(3)　281-285　2007

  38. 歯髄の潜在的硬組織形成能

    細矢明宏, 中村浩彰, 二宮 禎, 星 和人, 吉羽邦彦, 吉羽永子, 高橋将文, 岡部高弘, 佐原紀行, 山田博仁, 笠原悦男, 小澤英浩

    The BONE　21(4)　399-403　2007

  39. Alveolar bone regeneration after tooth transplantation into subcutaneous tissue

    HOSOYA Akihiro, NAKAMURA Hiroaki, YOSHIBA Kunihiko, YOSHIBA Nagako, YAMADA Hirohito, KASAHARA Etsuo, OZAWA Hidehiro

    49　42-42　2006/10/11

    ISSN： 0387-2343

  40. Osteoblasts prepare the osteoclast niche which determines the site of osteoclast generation.

    Y. Nakamichi, T. Mizoguchi, Y. Yamamoto, N. Udagawa, Y. Kobayashi, A. Hosoya, M. Nakamura, H. Ozawa, J. M. Penninger, N. Takahashi

    JOURNAL OF BONE AND MINERAL RESEARCH　21　S101-S101　2006/09

    ISSN： 0884-0431

  41. 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

  42. in vivo micro CT によるリセドロネートの骨吸収抑制効果の検討

    二宮 禎, 新井 嘉則, 中村 浩彰, 細矢 明宏, 関 あずさ, 高橋 直之, 小澤 英浩

    日本骨形態計測学会雑誌 = Journal of Japanese Society of Bone Morphometry　16　(2)　S104　2006/07/01

    ISSN： 0917-4648

  43. α-平滑筋アクチンの歯周組織発生過程における局在と歯槽骨形成との関連

    細矢 明宏, 中村 浩彰, 二宮 禎, 吉羽 邦彦, 脇谷 滋之, 山田 博仁, 笠原 悦男, 小澤 英浩

    日本骨代謝学会学術集会プログラム抄録集　24回　262-262　2006/07

    Publisher: (一社)日本骨代謝学会

    ISSN： 1349-0761

  44. 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

  45. Immunohistochemical Localization of α-SMA during rat molar tooth development

    HOSOYA Akihiro, NAKAMURA Hiroaki, YOSHIBA Kunihiko, YOSHIBA Nagako, YAMADA Hirohito, KASAHARA Etsuo, OZAWA Hidehiro

    48　59-59　2005/10/31

    ISSN： 0387-2343

  46. Morphological study for a mechanism of osteolysis by the human breast cancer cell MDA-MB-231.

    H Nakamura, T Hiraga, T Ninomiya, A Hosoya, M Yamaki, Y Arai, T Yoneda, H Ozawa

    JOURNAL OF BONE AND MINERAL RESEARCH　20　(9)　S217-S218　2005/09

    ISSN： 0884-0431

  47. Prostaglandin E-2 receptor (EP4) agonist stimulates osteoblasts and increases bone volume.

    T Ninomiya, H Nakamura, A Hosoya, Y Arai, N Sahara, K Yamaguchi, H Oida, H Ozawa

    JOURNAL OF BONE AND MINERAL RESEARCH　20　(9)　S352-S352　2005/09

    ISSN： 0884-0431

    eISSN： 1523-4681

  48. 硬組織形成とミネラル代謝研究の新展開 骨細胞外マトリックスの役割

    星 和人, 細矢 明宏, 小澤 英浩

    Journal of Oral Biosciences　47　(Suppl.)　68-68　2005/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

  49. ヒト歯根膜に由来する多能性幹細胞について

    細矢明宏

    The BONE　19(2)　236-237　2005

  50. 骨基質タンパクの局在における脱灰および固定の影響

    細矢明宏, 星 和人, 佐原紀行, 二宮 禎, 赤羽章次, 川本忠文, 小澤英浩

    The BONE　19(3)　251-255　2005

  51. Immunohistochemical Study of Hard Tissue Formation in a Subcutaneously-transplanted Rat Dental Pulp

    HOSOYA Akihiro, YOSHIBA Kunihiko, YOSHIBA Nagako, YAMADA Hirohito, KASAHARA Etsuo, OZAWA Hidehiro

    47　27-27　2004/10/18

    ISSN： 0387-2343

  52. Gene Expression and Protein Localization of MMP-2, -9, MT1-MMP and TIMP-1, -2, -3 During Mouse Molar Tooth Development

    YOSHIBA Nagako, YOSHIBA Kunihiko, OKIJI Takashi, HOSOYA Akihiro, OZAWA Hidehiro

    47　195-195　2004/10/18

    ISSN： 0387-2343

  53. マウス切歯発生過程におけるTIMPsの発現

    吉羽 永子, 吉羽 邦彦, 興地 隆史, 細矢 明宏, 小澤 英浩

    Journal of oral biosciences　46　(5)　451-451　2004/09/01

    Publisher: 歯科基礎医学会

    ISSN： 1349-0079

  54. エナメル器の細胞における転写調節因子Sp3,4局在について

    中村 浩彰, 二宮 禎, 細矢 明宏, 八巻 真理子, 小澤 英浩

    Journal of oral biosciences　46　(5)　452-452　2004/09/01

    Publisher: 歯科基礎医学会

    ISSN： 1349-0079

  55. レーザー光照射による大腿骨骨量変化の三次元的解析

    二宮 禎, 細矢 明宏, 西坂 剛, 中村 浩彰, 小澤 英浩

    Journal of oral biosciences　46　(5)　462-462　2004/09/01

    Publisher: 歯科基礎医学会

    ISSN： 1349-0079

  56. 歯髄の硬組織形成機構に関する微細構造学的研究 ラット切歯歯髄皮下移植実験モデルを用いた検討

    細矢 明宏, 中村 浩彰, 星 和人, 佐原 紀行, 二宮 禎, 吉羽 邦彦, 吉羽 永子, 小澤 英浩

    Journal of Oral Biosciences　46　(5)　377-377　2004/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

  57. 未固定非脱灰凍結切片法による骨基質タンパクの局在

    細矢 明宏, 星 和人, 佐原 紀行, 赤羽 章司, 川本 忠文, 矢ヶ崎 裕, 小澤 英浩

    解剖学雑誌　79　(2)　81-81　2004/06

    Publisher: (一社)日本解剖学会

    ISSN： 0022-7722

  58. 歯根膜破骨細胞の分化と成熟

    川原 一郎, 細矢 明宏, 小澤 英浩

    歯科基礎医学会雑誌　45　(5)　298-298　2003/09/01

    Publisher: 歯科基礎医学会

    ISSN： 0385-0137

  59. モルモット臼歯の軟骨様セメント質の微細構造的特徴とその形成過程

    佐原 紀行, 森山 敬太, 影山 徹, 三澤 康子, 細矢 明宏, 小澤 英浩

    歯科基礎医学会雑誌　45　(5)　332-332　2003/09/01

    Publisher: 歯科基礎医学会

    ISSN： 0385-0137

  60. ラット皮下移植歯髄の硬組織誘導能に関する免疫組織化学的研究

    細矢 明宏, 星 和人, 吉羽 邦彦, 吉羽 永子, 笠原 悦男, 小澤 英浩

    歯科基礎医学会雑誌　45　(5)　295-295　2003/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 0385-0137

  61. 未固定非脱灰及び未固定脱灰切片における骨基質タンパクの局在

    細矢 明宏, 星 和人, 佐原 紀行, 川本 忠文, 矢ヶ崎 裕, 小澤 英浩

    歯科基礎医学会雑誌　45　(5)　300-300　2003/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 0385-0137

  62. An immunohistochemical study of hard tissue formation in the pulp cavity of rat molar after transplantation into subcutaneous tissue.

    A. Hosoya, K. Yoshiba, N. Yoshiba, K. Hoshi, M. Iwaku, H. Ozawa

    JOURNAL OF DENTAL RESEARCH　82　B252-B252　2003/06

    ISSN： 0022-0345

  63. The cancellous bone formation by activation of EP4

    N Sahara, M Tanaka, K Yamaguchi, A Hosoya, T Ninomiya, H Ozawa

    BONE　32　(5)　S138-S138　2003/05

    ISSN： 8756-3282

  64. Immunohistochemical localization of bone matrix proteins in frozen and undecalcified sections

    A Hosoya, N Sahara, K Hoshi, T Kawamoto, H Ozawa

    BONE　32　(5)　S104-S104　2003/05

    ISSN： 8756-3282

  65. ラット臼歯の皮下移植後に観察される歯髄腔内硬組織形成

    細矢 明宏, 小澤 英浩, 吉羽 邦彦, 吉羽 永子, 岩久 正明, 星 和人

    THE BONE　17　(2)　3-6　2003/03

    Publisher: (株)メディカルレビュー社

    ISSN： 0914-7047

  66. ラット臼歯の皮下移植後に形成される歯髄腔内硬組織形成

    細矢明宏, 吉羽邦彦, 吉羽永子, 星和人, 岩久正明, 小澤英浩

    The BONE　17(2)　107-110　2003

  67. mechanical stressが糖尿病ラットの歯槽骨におよぼす影響

    三嶋 直之, 白川 正順, 細矢 明宏, 佐原 紀行, 小澤 英浩

    歯科基礎医学会雑誌　44　(5)　434-434　2002/09/20

    Publisher: 歯科基礎医学会

    ISSN： 0385-0137

  68. PGE2のreceptor(EP4)agonistによる骨形成

    佐原 紀行, 細矢 明宏, 松浦 幸子, 小澤 英浩

    歯科基礎医学会雑誌　44　(5)　436-436　2002/09/20

    Publisher: 歯科基礎医学会

    ISSN： 0385-0137

  69. Prostaglandin E EP4 receptor agonist induces the bone formation by an alteration of the osteoblast and osteoclast dynamic state.

    M Tanaka, N Sahara, T Katayama, K Yamaguchi, A Hosoya, N Mishima, S Matsuura, H Ozawa

    JOURNAL OF BONE AND MINERAL RESEARCH　17　S441-S441　2002/09

    ISSN： 0884-0431

  70. ラット切歯先端部硬組織の免疫組織化学的研究

    細矢 明宏, 星 和人, 吉羽 邦彦, 吉羽 永子, 笠原 悦男, 小澤 英浩

    歯科基礎医学会雑誌　44　(5)　417-417　2002/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 0385-0137

  71. An immunohistochemical study of hard tissue formation in the pulp cavity of rat molar after transplantation into subcutaneous tissue

    Hosoya Akihiro

    Niigata dental journal　32(1)　(1)　97-98　2002

    Publisher: Niigata University

    ISSN： 0385-0153

  72. 未固定非脱灰凍結切片法-特に骨組織観察の実際と利点について-

    細矢明宏, 佐原紀行, 小澤英浩

    The BONE　16(5)　427-431　2002

  73. ラット臼歯皮下移植実験モデルにおける歯髄腔内硬組織形成に関する免疫組織化学的研究

    細矢 明宏, 吉羽 邦彦, 吉羽 永子, 星 和人, 岩久 正明, 小澤 英浩

    歯科基礎医学会雑誌　43　(5)　569-569　2001/08

    Publisher: (一社)歯科基礎医学会

    ISSN： 0385-0137

  74. 歯髄の石灰化に関する免疫組織化学的研究 ラット臼歯皮下移植実験モデルを用いた検討

    細矢 明宏, 吉羽 邦彦, 吉羽 永子, 星 和人, 岩久 正明, 小澤 英浩

    日本歯科保存学雑誌　44　(春季特別)　21-21　2001/04

    Publisher: (NPO)日本歯科保存学会

    ISSN： 0387-2343

  75. ラット臼歯の皮下移植後に形成される歯髄腔内硬組織に関する免疫組織化学的研究

    細矢 明宏, 吉羽 邦彦, 吉羽 永子, 星 和人, 岩久 正明, 小澤 英浩

    新潟歯学会雑誌　30　(2)　268-268　2000/12

    Publisher: 新潟歯学会

    ISSN： 0385-0153

Show all ︎Show first 5

Books and Other Publications 2

  1. 口腔組織・発生学 第3版

    前田, 健康, 網塚, 憲生, 中村, 浩彰

    医歯薬出版　2024/01

    ISBN: 9784263456767

  2. 硬組織研究ハンドブック

    MDU出版会　2005

Research Projects 45

  1. α-平滑筋アクチン陽性筋上皮細胞を用いた唾液腺再生

    細矢 明宏, 建部 廣明, 谷村 明彦, 溝口 利英

    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: 北海道医療大学

    2025/04/01 - 2028/03/31

  2. 歯根膜幹細胞の骨芽細胞分化制御メカニズムの解明

    建部 廣明, 志茂 剛, 細矢 明宏

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 北海道医療大学

    2024/04/01 - 2027/03/31

  3. Senescent cell niche: Analysis of the Aging of bone regenerative capacity in 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 (B)

    Institution: Tokyo Dental College

    2024/04/01 - 2026/03/31

  4. Elucidation of the Mechanism of Vitamin D Receptor-Responsive Odontoblast Differentiation

    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: Health Sciences University of Hokkaido

    2023/04/01 - 2026/03/31

  5. Senescent cell niche: Analysis of aging mechanism of bone regeneration capacity in 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 (B)

    Institution: Tokyo Dental College

    2023/04/01 - 2026/03/31

  6. Molecular Basis of Hedgehog Signaling and New Therapeutic Strategies for Cancer induced Bone-Destruction

    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: Health Sciences University of Hokkaido

    2022/04/01 - 2026/03/31

  7. 癌の骨破壊病変に対するHedgehogシグナルの分子基盤の構築と新たな治療戦略

    志茂 剛, 吉田 祥子, 堀江 尚弘, 奥井 達雄, 建部 廣明, 平木 大地, 谷村 明彦, 長塚 仁, 細矢 明宏, 高畠 清文

    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: 北海道医療大学

    2022/04/01 - 2026/03/31

  8. 株化歯根膜幹細胞の樹立と骨芽細胞分化メカニズムの解明

    細矢 明宏, 吉羽 邦彦, 荒川 俊哉, 建部 廣明, 溝口 利英

    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: 北海道医療大学

    2022/04/01 - 2025/03/31

  9. 歯髄-象牙質の治癒・再生過程におけるCD146陽性幹細胞の局在と分化機序の解明

    渋井 徹, 入江 一元, 細矢 明宏

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 北海道医療大学

    2022/04/01 - 2025/03/31

  10. 歯髄の創傷治癒・再生過程におけるGli1陽性幹細胞の動態と分化誘導機構の解明

    吉羽 邦彦, 吉羽 永子, 枝並 直樹, 細矢 明宏, 入江 一元

    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: 新潟大学

    2021/04/01 - 2024/03/31

    More details Close

    歯の保存には歯髄の保護・保存が重要であり、直接覆髄や一部生活歯髄切断など歯髄保存療法が、また失われた歯髄に対しては再生歯内療法が試みられている。しかし根管内に形成される硬組織はセメント質あるいは骨様組織であり、理想的な「象牙質・歯髄複合体の再生」には至っていない。また、より迅速かつ確実な処置法の開発が望まれている。本研究では、歯髄の創傷治癒・再生過程において中心的役割を果たすと考えられている間葉系幹細胞の動態について、転写因子Gli1発現をマーカーとして細胞系譜解析により検索するとともに、覆髄材・根管充填材として注目されているバイオセラミックス配合材料の歯髄創傷治癒に与える影響について検討した。 遺伝子改変(Gli1-CreERT2/Tomato)マウスにおいて、Gli1陽性細胞は歯根膜および歯髄の血管周囲に散在性に認められること、また、臼歯歯根膜から分取されたGli1陽性細胞はコロニー形成能、多分化能を示し幹細胞特性を持つことが明らかにされた。これらの結果から、再生歯内療法応用後の治癒過程、特に硬組織形成におけるGli1陽性細胞の関与が示唆された。一方、バイオセラミックス配合覆髄材・根管充填材のin vitro・in vivoにおけるアパタイト析出能を検討した結果、すべての被験材料は疑似体液中でその表面にCa-Pを含むアパタイト様構造物を析出させたが、ラット皮下移植実験では、材料間にその析出能の差異が認められた。また、レジン含有ケイ酸カルシウム（MTA）系セメントは断髄後、CD68陽性マクロファージの持続的な浸潤と修復象牙質形成の遅延が観察され、材料選択の重要性が示唆された。

  11. Shh-Gli1応答性歯根膜幹細胞分化機構の解明と歯槽骨再生への応用

    建部 廣明, 建部 二三, 志茂 剛, 入江 一元, 細矢 明宏

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 北海道医療大学

    2020/04/01 - 2023/03/31

    More details Close

    口腔インプラント治療においては、インプラント体を埋入するための骨量確保が重要であり、近年では骨芽細胞分化機構を応用した骨再生の取り組みも行われている。歯根膜に存在する幹細胞マーカーとしてGli1陽性細胞が報告されている。Gli1はSonic hedgehog（Shh）の下流因子として知られているが、骨芽細胞分化とどのような関連があるかは明らかにされていない。歯槽骨を形成する骨芽細胞は、組織幹細胞から分化すると考えられる。しかし、歯根膜に存在する組織幹細胞における維持調節機構は不明な点が多い。我々はこれまで、フェイトマッピング解析法を用い、歯根膜組織の未分化細胞が転写因子Gli1を発現し、幹細胞特性を有することを見い出した。しかしGli1は骨芽細胞分化とどのような関連があるかは明らかにされていない。また、Gli1の上流にはSonic hedgehog（Shh）をはじめとする様々な因子が報告されているが、それらが骨芽細胞分化にどのような影響を与えているか明らかにされていない。そこで、本研究では、Gli1陽性細胞の特性を理解するため、Gli1因子の上流に存在する因子と骨芽細胞分化との関連について検討した。今年度は、Gli1の上流に位置する B cell-specific moloney murine leukemia virus integration site 1(Bmi1)と骨芽細胞分化との関連を実験動物を用いて検討し、Bmi1が骨芽細胞分化に関係することを論文発表した。また、Shhと骨芽細胞分化との関係については、抜歯後のShh-CreERT2-Tomatoマウスを用いた検討を行い、学会発表を行なった。

  12. In vivo機能解析による唾液腺の代償性機能亢進機構の解明と分泌亢進誘導

    根津 顕弘, 森田 貴雄, 細矢 明宏

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 北海道医療大学

    2020/04/01 - 2023/03/31

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    唾液腺は片側が機能不全に陥ると残った唾液腺が代償性に肥大し、低下した唾液分泌を補っている。我々は生きた動物の唾液腺のCa2+応答と唾液分泌in vivo機能解析法により、片側障害が残った唾液腺を「機能亢進腺」に誘導することを明らかにした。本研究課題では「片側唾液腺障害によって起こる唾液腺の代償性機能亢進はどのような情報伝達により誘導されるのか、また機能亢進を起こすしくみは何か?」を明らかにすることを目的とする。また得られた結果をもとに、薬物や遺伝子制御により人為的に「唾液が出やすくなる唾液腺」の誘導を試みる。 本年度は、網羅的解析により変化が認められた57遺伝子のうち、結紮7および21日後の反対側顎下腺で有意に発現変化する可能性を示す新たな4遺伝子について解析を行った。その結果7日後の機能亢進腺で別の時間遺伝子の発現上昇が確認され、機能亢進発現の新たなマーカー遺伝子候補を見出した。 さらに唾液分泌と血流動態の関係について解析を行った。Ca2+と血流動態の同時測定を用いてアセチルコリン（ACh）の持続投与により顎下腺全体で見られるCa2+振動と血流振動が起こることを初めて明らかにした。また、このCa2+と血流振動の発生には自律神経系の調節よりも、血中の血管収性オータコイドの関与が大きいことを見出した。さらに水チャネル（AQP5）低発現ラットを用いた実験により、AQP5発現量は強い刺激による水分泌量を決定すること、またACh刺激による唾液腺の血流上昇が高いラットでは唾液分泌におけるAChに対する感受性が亢進していることを明らかにした。この結果は機能亢進腺でAChに対する血流上昇反応が亢進している可能性を示しており、今後は機能亢進腺における血流動態関連に関する検討も行う予定である。（研究協力者：郷賢治、Tahmina Akter）

  13. Identification of novel dental pulp stem cells and analysis of their regulatory mechanisms of differentiation

    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 Dental College

    2020/04/01 - 2023/03/31

  14. Osteoblast differentiation of periodontal ligament stem cells expressing Gli1/Tomato fluorescence

    HOSOYA Akihiro

    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: Health Sciences University of Hokkaido

    2019/04/01 - 2022/03/31

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    The periodontal ligament (PDL) contains mesenchymal stem cells (MSCs) that can differentiate into osteoblasts, cementoblasts, and fibroblasts. Nevertheless, the distribution and characteristics of these cells remain uncertain. Therefore, in the present study, the differentiation ability of Gli1-positive cells was examined using iGli1/Tomato mice. In 8-week-old iGli1/Tomato mice, Gli1/Tomato-positive cells were quiescent. However, these cells exhibited high CFU-F activity and were capable of multi-differentiation in vitro. Additionally, after transplantation of teeth of iGli1/Tomato mice into the hypodermis of wild-type mice, Tomato fluorescence indicating the progeny of Gli1-positive cells was detected in the osteoblasts of the regenerated bone. These results demonstrate that Gli1-positive cells in the PDL were MSCs and could contribute to the alveolar bone regeneration.

  15. Elucidation of odontoblast differentiation factors by fate mapping analysis and its application to dentin regeneration therapy Competitive

    IRIE Kazuharu

    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: Health Sciences University of Hokkaido

    2018/04/01 - 2021/03/31

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    Fate mapping analysis with an inducible Cre / loxP system was performed to investigate the process of differentiation from Gli1-positive dental pulp stem cells into hard tissue-forming cells and odontoblasts. After administration of tamoxiphen to 4-week-old mice, the first molar tooth was removed and transplanted into the litter, and Tomato-labeled cells were arranged on the surface of the hard tissue formed in the pulp, and Gli1-positive cells were intradentally. It was shown that it had differentiated into hard tissue-forming cells. It was confirmed that these Gli1-positive cells can form colonies and differentiate into chondrocytes, osteoblasts, and adipocytes, and have stem cell characteristics. Furthermore, it was suggested that these cells may be CD146 positive in the dental papilla and pulp in the early stage of dentin formation. It was confirmed that it has stem cell characteristics.

  16. Tissue-resident macrophages in dental pulp regulate the microenvironment for reparative dentine formation Competitive

    Nakamura Hiroaki

    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: Matsumoto Dental University

    2017/04/01 - 2020/03/31

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    We investigated the localization of Wnt-related molecules and F4/80-positive macrophages in the process of reparative dentin formation. After directly pulp-capping with MTA cement in the upper first molars of mice, reparative dentin formation was confirmed 14 days after direct pulp capping by micro-CT analysis. Histological analysis revealed that odontoblasts arrayed on the surface of reparative dentin were positive for Wnt3a and Wnt10a.b-catenin was localized in their nucleus. Additionally, F4/80-positive macrophages in the pulp expressed Wnt10a. The localization of b-catenin was found in the nucleus of pulp cells surrounding macrophages. These results suggest that odontoblast- and macrophage-derived Wnt were involved in the reparative odontoblast differentiation.

  17. Analysis of reparative dentin formation regulated by dental pulp stem cells using a fate mapping approach Competitive

    Mizoguchi Toshihide

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

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

    2017/04/01 - 2020/03/31

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    Tertiary dentin formation is induced in response to dental cavity preparation for dental treatment. In this biological process, cavity preparation induces odontoblastic cell death and fewer odontoblasts are thus regenerated from dental pulp stem cells, resulting in induced reparative dentin formation. However, the relationship between odontoblastic cell death and the regulation of tertiary dentin formation is unclear. In this study, we examined the effects of odontoblastic depletion on dentinogenesis activation using genetically modified mice. We found that dentin formation increased in response to odontoblastic cell death. This result suggests that there is a dental pulp niche environment regulated by odontoblastic cell death and that this regulatory network is essential for the activation of reparative dentin formation.

  18. A study on the mechanisms of induction and differentiation of stem cells during wound healing and regeneration of dentin-pulp complex Competitive

    YOSHIBA Kunihiko

    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: Niigata University

    2016/04/01 - 2020/03/31

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    This study aimed to elucidate the mechanism of dental pulp wound healing and reparative dentinogenesis. We investigated the cellular events and expression of related factors after direct pulp capping or pulpotomy. The results suggested that α-SMA-positive myofibroblasts are progenitors of odontoblast-like cells and that TGF-β1 and EDA-fibronectin are involved in their differentiation. In addition, bone marrow-derived mesenchymal cells, fibrocytes, appeared transiently in the early stages and M2 phenotype macrophages colocalized with Schwann cells in healthy as well as inflamed pulp. It was suggested that various types of cells are involved in pulp wound healing and repair process.

  19. Elucidation of the mechanism of bone-resorption in osteoclasts regulated by Pkn3. Competitive

    Uehara Shunsuke

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

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

    Institution: Matsumoto Dental University

    2016/04/01 - 2019/03/31

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    Osteoclasts are responsible for bone resorption. In inflammatory disease such as arthritis and periodontitis leads to bone destruction due to the excess bone-resorbing activity of osteoclasts. We investigated roles of Wnt5a, a cytokine, in the osteoclast function. We have shown that Wnt5a-Ror2 signaling promotes osteoclast function through the activation of Daam2-Rho-protein kinase N3 (Pkn3)-c-Src signaling pathways.

  20. Roles Gli1-positive dental pulp stem cells during dentin regeneration Competitive

    Hosoya Akihiro

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

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

    2016/04/01 - 2019/03/31

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    Although pluripotent stem cells exist in dental pulp, the characteristics of these cells and the mechanisms of their differentiation into odontoblasts are controversial. In this study, we found that cells expressing the transcription factor Gli1 localized around the blood vessels in the dental pulp of mature mouse molar. In addition, these cells had high CFU-F activity as well as multipotency into osteoblasts, chondrocytes, and adipocytes in vitro. We also showed that Gli1-positive cells proliferate and differentiate into reparative odontoblasts during dentin regeneration after cavity formation. Therefore, these results suggest that Gli1 is a useful marker for dental pulp stem cells in the research of pulp biology.

  21. Functional roles of the cancer stem cell marker EpCAM in cancer bone metastasis Competitive

    Hiraga Toru

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

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

    Institution: Matsumoto Dental University

    2015/04/01 - 2018/03/31

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    In the current study, we examined the roles of epithelial cell adhesion molecule (EpCAM) in the development of cancer bone metastasis. EpCAM-negative (EpCAMneg) and EpCAM-positive (EpCAMpos) populations isolated from cancer cell lines exhibited mesenchymal and epithelial phenotypes, respectively. Flow cytometric analysis revealed that EpCAMpos, but not EpCAMneg, cells possessed self-renewal and differentiation potentials. Tumorsphere formation in vitro and tumorigenicity in the mammary fat pad of mice were significantly greater in EpCAMpos cells than in EpCAMneg cells. Furthermore, the development of bone metastases was markedly increased in mice inoculated with EpCAMpos cells. These results suggest that the expression of EpCAM in cancer cells is associated with cancer stem-like phenotypes, which contribute to the promotion of bone metastases by enhancing tumorigenicity.

  22. Role of M2 macrophages in reparative dentin formation and development of new endodontic regerative treatment Competitive

    NAKAMURA Hiroaki

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: Matsumoto Dental University

    2015/04/01 - 2017/03/31

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    We examined immunohisotochmical localization of Wnt signaling molecules in the process of reparative dentin formation after cavity preparation in order to clarify a role of M2 macrophages in the odontoblastic differentiation of pulp cells. At 3 days after cavity preparation, macrophages showed immunoreactivity for Wnt10a and GPR177. At 7 days, localization of b-catenin is seen in nucleus of odontoblasts contacting reparative dentin. These results indicate that canonical Wnt signal plays an important role in reparative dentin formation. Reagents activating canonical Wnt signal might be usuful for new endodontic treatment.

  23. The study of the mandibular condyle regeneration using the cell sheet Competitive

    NAKATSUKA Michiko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

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

    Institution: Osaka Dental University

    2014/04/01 - 2017/03/31

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    To elucidate the chondrocyte differentiation ability of bone marrow-derived mesenchymal stem cells, we experimented with the cells that formed spheroids in vitro. The cells were cultured into cryo vials (100000 cells/ml) and incubated in culture media (1% FBS, 1% insulin - transferrin - selenite (ITS), dexamethasone (0.1μM), sodium pyruvate (1mM), TGFβ-3 (10 ng/ml-containing). The differentiation of the spheroids that the cells formed (day 21 specimen) was assayed. Cell differentiation was evaluated by Alcian blue staining. We also examined immunohistochemically by using Sox9 and aggrecan antibodies. In the experimental group,these structures showed positive reaction of Alcian blue, Sox9, and aggrecan. On the other hand, there were no evidences of chondrocyte differentiation in the control group. Therefore, these results suggest that spheroid formation of bone marrow-derived mesenchymal stem cells might be useful in chondrocyte regeneration therapy.

  24. How is the formation site of osteoclasts determined? Competitive

    Takahashi Naoyuki, Nakamichi Yuko, Mizoguchi Toshihide, Hosoya Akihiro, Kobayashi Yasuhiro, Kawahara Ichiro, Udagawa Nobuyuki

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: Matsumoto Dental University

    2014/04/01 - 2016/03/31

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    Why do osteoclasts formed only in the bone? It has been considered “ because osteoblasts express osteoclast differentiation factor RANKL and M-CSF." However, when RANKL and M-CSF are administered intraperitoneally to RANKL-deficient mice and M-CSF-deficient op/op mice, respectively, osteoclasts appear only in bone tissue. This indicates that expression sites of RANKL and M-CSF do not determine the formation site of osteoclasts. In the present study, we showed that osteoclast precursors (OP) which highly express RANK (RANK-abundant OP, rOP) are detected only in the bone tissue. Localization of rOP is shown to determine the formation site of osteoclasts.

  25. The effect of SUMOylation on bone formation in mouse Competitive

    AKIRA Yukita, NAKAMURA Hiroaki, HOSOYA Akihiro, ITO Yuzuru, HOSOYA Akihiro

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

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

    2012/04/01 - 2015/03/31

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    We investigated the effect of SUMOylation on BMP-induced osteoblastic differentiation using various cell lines. Inhibition of SUMOylation suppressed the osteoblastic differentiation induced by BMP treatment in the MC3T3E1 cells, which derived from mouse calvaria, while enhanced it in ST2 mouse bone marrow derived stromal cells and murine fibroblasts (C3H10T1/2 cells). This Data shows that the effect of SUMOylation on osteoblastic differentiation might change depending on degree of osteoblasts.

  26. Functional analysis of Osterix in immature odontoblasts for cell differentiation Competitive

    HOSOYA Akihiro, NAKAMURA Hiroaki, HIRAGA Toru, YUKITA Akira

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

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

    Institution: Matsumoto Dental University

    2012/04/01 - 2015/03/31

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    Osterix was localized in odontoblasts just beginning dentin matrix secretion during the processes of dentin formation and regeneration. However, as dentin formation progressed, this immunoreactivity decreased in intensity. In addition, although osteoblasts that were differentiated from dental pulp cells maintained the reactivity of Osterix, this reactivity was not detected in mature odontoblasts originated from pulp cells. Therefore, these results suggest that temporary expression of Osterix in odontoblast-lineage cells might play important roles in odontoblast differentiation and regeneration.

  27. 骨代謝共役を担うWntシグナルの解明

    高橋 直之, 小出 雅則, 小林 泰浩, 中道 裕子, 中村 浩彰, 田口 明, 細矢 明宏, 上原 俊介

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(A)

    Category: 基盤研究(A)

    Institution: 松本歯科大学

    2013/04/01 - 2014/03/31

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    骨吸収と骨形成は厳格に共役しているが、分子機構は不明である。我々は、破骨細胞の前駆細胞(QOP)を同定した(J Cell Biol, 2009; Proc Natl Acad Sci USA, 2012)。また、骨芽細胞が産生するWnt5a は受容体Ror2 を介して、QOP から破骨細胞への分化を促進することを見出した(Nature Med, 2012)。さらに最近、破骨細胞は、①骨芽細胞の分化を誘導するWnt を発現する可能性、②骨細胞が発現する骨形成阻害因子Sclerostin（Wnt 抑制因子）産生を抑制する可能性を見出した。すなわち破骨細胞は骨芽細胞を活性化するWnt を産生するとともに、Sclerostin 分泌抑制を介し骨形成を促進することが示唆された。本研究では、破骨細胞と骨芽細胞を制御するWnt シグナルの全容を解明し、骨代謝共役機構を明らかにすることを目的とした。 破骨細胞と骨芽細胞の相互作用を解析するためにOPG欠損マウスを本学から熊本大学に搬送した。現在、熊本大学で形態学的に破骨細胞の分化状況を解析中である。

  28. The mechanisms of bone-selective cancer metastases based on the pre-metastatic bone niche hypothesis

    HIRAGA TORU, HOSOYA Akihiro, NINOMIYA Tadashi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: Matsumoto Dental University

    2011 - 2013

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    In the present study, we examined whether the changes in bone marrow cell population in tumor-bearing mice affect the development of bone metastases. Both in the bone marrow in the tumor-bearing mice and in the bone marrow with tumor metastases, the ratio of Gr-1+/CD11b+ cells was markedly increased. Furthermore, the inoculation of tumor cells with Gr-1+/CD11b+ cells isolated from tumor-bearing mice enhanced the formation of subcutaneous tumors. However, bone metastases were not increased in the presence of subcutaneous tumors. Further studies are required to fully define the relationship between bone marrow Gr-1+/CD11b+ cells and the development of bone metastases.

  29. We elucidated osteogenic capacity of CD90-posidive cells and side population (SP) cells derived from bone marrow stromal cells to establish the hard tissue regeneration therapy. Most of bone marrow stromal cells expressed CD90, one of mesenchymal stem cell markers, and contained 0.5% SP cells. CD90-positive cells and SP cells could differentiate osteoblastic cells in in vitro and in vivo. However, we could not clarify specific genes of osteoprogenitor cells.

    NAKAMURA Hiroaki, HOSOYA Akihiro, YUKITA Akira, NINOMIYA Tadashi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: Matsumoto Dental University

    2011 - 2012

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    We elucidated osteogenic capacity of CD90-posidive cells and side population (SP) cells derived from bone marrow stromal cells to establish the hard tissue regeneration therapy. Most of bone marrow stromal cells expressed CD90, one of mesenchymal stem cell markers, and contained 0.5% SP cells. CD90-positive cells and SP cells could differentiate osteoblastic cells in in vitro and in vivo. However, we could not clarify specific genes of osteoprogenitor cells.

  30. Roles of cancer stem cells in the development and progression of cancer metastasis to bone

    HIRAGA Toru, HOSOYA Akihiro, NINOMIYA Tadashi, KOBAYASHI Yasuhiro

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

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

    Institution: Matsumoto Dental University

    2009 - 2012

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    Bone is one of the most preferential sites for cancer metastasis; however, the precise mechanisms are still unclear. An increasing body of evidence suggests that cancers contain a small subset of their own stem-like cells called cancer stem cells (CSCs), which play critical roles in the initiation, maintenance and relapse of tumors. In this study, we studied the role of CSCs in cancer metastasis to bone. Flow cytometric analysis revealed the existence of CSC marker-positive cells in several kinds of cancer cell lines. Those cells exhibited some of the CSC-like properties in vitro and in vivo. However, the bone-metastatic potential of side population (SP) cells, which has been shown to enrich CSCs in several types of cancer, was similar to that of non-SP cells. Further studies are required to clarify the contribution of CSCs to cancer bone metastasis.

  31. Dentin regeneration by Thy-1-positive dental pulp cells

    HOSOYA Akihiro

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

    Category: Grant-in-Aid for Young Scientists (B)

    Institution: Matsumoto Dental University

    2010 - 2011

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    The majority of cells in the subodontoblastic layer express Thy-1.Therefore, to clarify the characteristics of cells in the subodontoblastic layer, the differentiation ability of Thy-1-positive cells into mineralizing cells was analyzed in vitro and in vivo. Following stimulation with BMP-2, Thy-1-positive dental pulp cells showed accelerated induction of ALP activity. Additionally, subcutaneous implantation of these positive cells induced numerous mineralized matrix formations. These results collectively suggest that Thy-1-positive dental pulp cells localized in the subodontoblastic layer have the ability to differentiate into hard tissue-forming cells.

  32. 歯根膜組織幹細胞の誘導と再生歯科医療の可能性

    中村 浩彰, 細矢 明宏, 雪田 聡, 二宮 禎

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 挑戦的萌芽研究

    Category: 挑戦的萌芽研究

    Institution: 松本歯科大学

    2009 - 2010

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    歯根膜細胞の再生歯科医療への応用の可能性について検討するために、組織幹細胞を多く含むSP(Side Population)細胞のin vivo移植実験を行い、その骨形成能について解析した。GFP(Green Fluorescent Protein)発現ラット臼歯の歯根膜細胞からSP細胞およびMP(Main Ppopulation)細胞を分離し、ハイドロキシアパタイト上で培養後、野生型ラットの皮下組織に移植した。移植4週目ではSP細胞移植群ではハイドロキシアパタイトに接してアリザリンレッド陽性の石灰化基質が形成され、骨シアロタンパク質、オステオポンチンを含む骨組織であることが免疫組織化学的に明らかとなった。また、GFP陽性細胞が骨組織に接して認められたことから、歯根膜細胞由来SP細胞が骨芽細胞に分化することが示唆された。一方、MP細胞の移植後4週では骨組織形成はほとんどみられなかった。SP細胞移植後12週では、骨組織量は増加し、骨基質内にみられる骨細胞がGFP陽性であったことから、歯根膜細胞由来SP細胞は骨細胞に最終分化することがわかった。さらに、骨基質には破骨細胞も接着して認められたことから、SP細胞によって形成された骨組織は正常な骨組織と同様にリモデリングされ、生体に適合した組織であることがわかった。本研究により、歯根膜由来SP細胞は骨芽細胞や骨細胞に分化して骨組織を形成することから、歯周組織再生医療において有用な細胞であること明らかとなった。しかし、幹細胞維持のために必須な遺伝子群については明らかにすることはできず、歯根膜組織幹細胞の誘導については今後の課題である。

  33. Analysis of molecular mechanism of carbon nanotube regulating bone metabolism

    MIZOGUCHI Toshihide, KOIDE Masanori, NAKAMICHI Yuko, YAMASHITA Teruhito, HOSOYA Akihiro, NINOMIYA Tadashi, UDAGAWA Nobuyuki, TAKAHASHI Naoyuki, NAKAMURA Hiroaki, OZAWA Hidehiro

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)

    Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)

    Institution: Matsumoto Dental University

    2008 - 2010

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    Since attention has paied to the use of carbon nanotubes as biomaterials in contact with bone, it is critical to understand the reaction of bone cells to carbon nanotubes. In the present studies, we revealed following things. (1) Multiwalled carbon nanotube (MWCTs) enlarged BMP-induced ectopic bone size in vivo. (2) MWCTs inhibited the osteoclastic differentiation from osteoclast precursors in BMP-induced ectopic bone. (3) MWCTs suppressed osteoclasogeness by inhibition of RANKL-induced nuclear translocation of NFATc1 in vitro. (4) MWCTs inhibit osteoclastic bone resorption and survival. (5) MWCTs enhanced calcification by osteoblasts in calcification medium. (6) Ca and Na deposited around the MWCNTs by calcification medium. (7) The ALP activity and the expression level of osteocalcin in osteoblasts were enhanced by high calcium concentrations in culture medium. These results indicated that MWCNTs have beneficial effect on bones when they are used as biomaterials.

  34. 造血幹細胞ニッチを介した癌の骨転移成立機構の解明

    平賀 徹, 細矢 明宏, 二宮 禎

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 挑戦的萌芽研究

    Category: 挑戦的萌芽研究

    Institution: 松本歯科大学

    2008 - 2009

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    骨への臓器特異的転移、および骨転移の成立・進展のメカニズム解明のために、本研究では骨転移における骨髄癌細胞ニッチの役割を明らかにすることを目的とし、「細胞接着分子を介した骨芽細胞と癌細胞の接着がニッチの形成に重要な役割を果たしている」との作業仮説を立てた。そのなかで、骨髄中の造血幹細胞ニッチの形成において、N-カドヘリンを介した骨芽細胞と造血幹細胞の接着が重要な役割を果たしていること、癌細胞のN-カドヘリンの発現が癌の悪性度と関連し、患者の予後と負の相関関係を示すことなどの報告から、特に細胞接着分子N-カドヘリンに注目し、研究を行った。昨年は、N-カドヘリンを過剰発現する癌細胞株、およびshRNAを用いたN-カドヘリンのノックダウン癌細胞株の樹立を行い、本年度は、これらの細胞を用い、in vivoの解析を行った。 1.N-カドヘリン過剰発現株およびノックダウン株のin vivoでの増殖能 N-カドヘリン過剰発現株およびノックダウン株の増殖能について、ヌードマウスへの移植により検討した結果、両者とも親株と比較して腫瘍増殖には差は認められなかった。 2.N-カドヘリン過剰発現株およびノックダウン株の骨転移能の比較 N-カドヘリン過剰発現株およびノックダウン株の骨転移能について、ヌードマウス左心室内移植モデルを用い検討した結果、こちらも両者とも親株と比較して腫瘍増殖には差は認められなかった。 今回のin vivoの実験結果からはいずれも癌細胞におけるN-カドヘリン発現の差異の影響を認めることは出来なかった。しかし、発現の増強および減弱の程度が十分であったかなどについては検討の余地があり、今後、継続して検討を進めていく予定である。

  35. An analysis of odontoblast differentiation mechanisms by using dental pulp SP cells

    HOSOYA Akihiro

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

    Category: Grant-in-Aid for Young Scientists (B)

    Institution: Matsumoto Dental University

    2008 - 2009

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    Although a number of studies suggest that many transcription factors participate in odontoblast differentiation, specific factors of odontoblast differentiation are still unknown. In the present study, immunohistochemical localizations for SUMO proteins and Osterix were visible in the immature odontoblasts ; however these immunoreactivities were reduced in the mature odontoblasts. These results demonstrate that reduction of expressions for SUMO proteins and Osterix in the mature odontoblasts might be necessary for dentin formation.

  36. A study on mechanisms of tissue repair and regeneration of the dentin-pulp complex

    YOSHIBA Kunihiko, YOSHIBA Nagako, HOSOYA Akihiro

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

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

    Institution: Niigata University

    2006 - 2008

  37. The relationship between cell proliferation and RANKL-induced osteoclastogenesis

    TAKAHASHI Naoyuki, MIZOGUCHI Toshihide, KOIDE Masanori, NAKAMURA Akihiro, NINOMIYA Tadshi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

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

    Institution: Matsumoto Dental University

    2006 - 2007

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    (1) In vitro analysis of the cell cycle in osteoclast progenitors : We have shown that cell cycle progression and withdrawal after the progression in osteoclast precursors are the two sequential events essential for RANKL-induced osteoclastogenesis. (2) The isolation and the analysis of QOPs: Cell cycle-arrested quiescent osteoclast precursors (QOPs) were identified as the committed osteoclast precursors in vitro. In vivo experiments showed that mononuclear cells expressing c-Fms and RANK but not Ki67 were detected along bone surfaces in the vicinity of osteoblasts in RANKL-deficient mice. They were identified as QOPs. (3) BMP transplantation experiments using RANKL(-/-) mice and OPG(-/-) mice : We examined the requirements for osteoclastogenesis using OPG(-/-) mice, RANKL(-/-) mice and a system involving BMP-induced ectopic bone formation. We have shown that osteoblasts also play important roles in osteoclastogenesis through offering the critical microenvironment for the action of RANKL. (4) Establishment of the Cre-lox P system for osteoclast specific deletion of target genes : We have succeeded to establish RANK Cre mice. We are now analyzing the Cre recombinase expression in osteoclastss. (5) Transgenic mice of cell cycle regulatory genes : We are advancing experiments on osteoclast niche, in stead of the production of the cycle regulatory gene transgenic mice. (6) Clinical application of anti-cancer drugs in bone diseases : We have shown that that taxanes have beneficial effects on the treatment of bone metastatic cancers. Administration of an anti-cancer drug, 5-fluorouracil, to mice induced myelosuppression, but QOPs survived and differentiated into osteoclasts in response to an active vitamin D_3 analog given to those mice. We have shown that QOPs pre-exist at the site of osteoclastogenesis and that osteoblasts play roles in the maintenance of QuOPs in the undifferentiated state. We found that c-Fos(-/-) mice have not osteoclast niche.

  38. ヒト造血系細胞再構成マウスを用いた歯槽骨リモデリング機構の解析

    小林 泰浩, 中道 裕子, 溝口 利英, 細矢 明宏

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 萌芽研究

    Category: 萌芽研究

    Institution: 松本歯科大学

    2006 - 2007

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    生体内における骨吸収の解析は,動物を用いて主に行われている.しかし,細胞培養系においてマウスとヒトのマクロファージ、マウスとヒトの破骨細胞を比較すると,生理活性物質に対する反応が異なることがある.プロスタグランジンE_2(PGE_2)は,マウスの破骨細胞の分化を促進するが,ヒト破骨細胞への分化を抑制する.本研究課題では,ヒト造血細胞由来の破骨細胞による骨吸収に及ぼすPGE_2の効果の検討を試みた.テトラサイクリン系抗生物質であるミノサイクリン(Mino)は、PGE_2の産生を介してヒトの骨吸収を抑制することが報告されている。H18年度にCD14陽性細胞およびマウス骨髄マクロファージをMinoで処理すると、RANKLで誘導する破骨細胞形成を抑制することを明らかにしている。Minoは、ヒト由来およびマウス由来マクロファージで、Cox2 mRNAを誘導しなかった。破骨細胞分化に必須な転写因子であるc-fosおよびNFATc1の発現を検討した。マクロファージをRANKLで刺激するとこれらの転写因子の発現は、著明に上昇した。しかし、マクロファージをRANKLと同時にMinoで処理すると両転写因子の発現が抑制された。これらの結果から、Minoは、PGE2産生を介さず、直接RANKLによるシグナルを遮断している可能性が示唆される。また、生体内においても、RANKL投与によって起こる骨吸収を抑制する結果を得ている。抗菌剤であるMinoが、骨吸収を抑制する可能性を示唆する。 マウスM-CSFとヒトRANKLが、ヒトCD14細胞の破骨細胞への分化を誘導するか検討した。しかし、マウスM-CSFはヒト破骨細胞を誘導しなかった。つまり、ヒト血液幹細胞をマウスに移植した場合、ヒト由来のM-CSFを投与する必要があると思われる。

  39. BMP antagonist調節による歯および骨の再生

    中村 浩彰, 二宮 禎, 細矢 明宏

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 萌芽研究

    Category: 萌芽研究

    Institution: 松本歯科大学

    2005 - 2006

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    現在の歯科医療においては、歯周病やインプラント治療に対処するために、歯周組織の再生をめざした歯科治療法の開発が望まれている。歯周組織は、歯小嚢由来の細胞がセメント芽細胞、骨芽細胞および線維芽細胞に分化し、生体内におけるそれぞれの細胞の位置的関係は厳密に決定されている。本年度は、歯周組織を構成する細胞の分化制御機構におけるにSOSTの役割を明らかにすることを目的に、その発生過程に注目して、SOSTおよびBMP関連分子の局在を検索した。歯周組織におけるBMP4局在は、主に線維芽細胞に認められ、SOST局在は、セメント芽細胞およびこれに近接する線維芽細胞に見られた。また、BMPを局所に保持するヘパラン硫酸プロテオグリカンは、歯根膜の細胞外基質に広く分布し、このプロテオグリカンを分解するヘパラナーゼ局在は、線維芽細胞およびマラッセ上皮遺残に認められた。一方、歯周組織の発生に伴い、骨芽細胞に特異的な転写調節因子Runx2とOsterix局在が、歯根膜細胞に認められ、特に骨芽細胞およびセメント芽細胞では、両者の共局在が核内に検出された。これらの結果から、セメント芽細胞、骨芽細胞および線維芽細胞の分化はBMP、これを局所に保持するヘパラン硫酸プロテオグリカンなどの細胞外基質、BMPの遊離に関与するヘパラナーゼ、BMP antagonistであるSOSTなどにより複雑に制御されているものと考えられた。本萌芽研究において歯や骨の発生過程には、BMPとそのアンタゴニストであるSOSTなどが細胞分化および形態決定に重要な役割を担っていることが明らかとなり、再生歯科医療においてもこれらの作用を考慮することが必要であることが示唆された。

  40. 摘出歯髄を用いた硬組織形成機構の解明

    細矢 明宏

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 若手研究(B)

    Category: 若手研究(B)

    Institution: 松本歯科大学

    2005 - 2006

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    歯髄の潜在的硬組織形成能を検討する目的で,GFP発現ラット切歯歯髄を野生型ラット皮下へ他家移植し,移植後の硬組織形成を免疫組織化学的に観察した。移植7日後,多くの細胞を含有した石灰化硬組織が歯髄辺縁部に形成され,14日後には歯髄のほぼ全域に石灰化が進行した。この新生硬組織はオステオカルシン,オステオポンチンおよび骨シアロタンパクの免疫局在を示したが,象牙質シアロタンパクの局在は認められなかったため,骨に類似した特性を有していた。また,この硬組織表面に配列する細胞はGFPの陽性反応を示したことから,歯髄細胞は象牙質が含有するBMP等の成長因子が無くとも独自の誘導能で硬組織を形成し,骨に類似した硬組織を形成することが明らかとなった。 次に,周囲に既存の象牙質が存在する条件下における歯髄の硬組織形成能を検討した。GFPラット臼歯を野生型ラット抜歯窩へ再植すると,14日後以降,歯髄腔内に象牙質シアロタンパク陽性または陰性の象牙質様または骨様の硬組織が形成された。またGFPは,象牙質様組織表面の全ての細胞で陽性反応を示したが,骨様組織表面では陽性細胞と陰性細胞が混在していた。以上の結果より,歯髄の周囲に象牙質が存在する環境下では,歯髄細胞は象牙質または骨に類似した2種の硬組織を形成することが明らかとなった。さらに,歯髄組織は,外部から進入した間葉細胞を骨芽細胞様細胞へと分化誘導することが明らかとなった。 本研究より,歯髄細胞は象牙芽細胞のみならず骨芽細胞へと分化する能力を持つことが明らかとなった。従って,歯髄組織は硬組織誘導活性を持つ細胞および物質を有する組織として,再生工学における応用が期待される。

  41. Ca^<2+> kinetics in mature osteoclast

    YAMAKI Mariko, OZAWA Hidehiro, TAKAHASHI Naoyuki, SAHARA Noriyuki, HOSOYA Akihiro

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

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

    Institution: Matsumoto Dental University

    2004 - 2005

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    Osteoclasts play an important role in the metabolism of both organic and inorganic components in bone via the following steps-osteoclasts originate from bone marrow cells, differentiate with the aid of osteoblasts, fuse to each other and form mature, multi-nuclear gigantic cells, attach onto a bone surface with many podosomes (i.e. fibrous actin (F-actin^1) and integrin complexes), form actin rings, develop projecting structures (called ruffled borders), excrete substances including acids and proteolytic enzymes from the ruffled borders, solubilize bone, and leave resorption lacunae on the bone surface. Actin rings and ruffled borders are the morphological hallmarks of mature osteoclasts, and are therefore routinely used to identify mature osteoclasts. Osteoclasts undergo ‘transcytosis' of organic components, such as collagen, that are thus solubilized from bone via the following steps-the cells absorb the organic components via endocytosis at the ruffled borders, in-cell transport these components to the apical membrane side of the cell, and perhaps expel (i.e.evacuate) them from the apical membrane toward the extracellular space. Thus, osteoclasts play a central role throughout the metabolism of organic components in bone-not only in the solubilization from bone but also in transcytosis steps (i.e. endocytosis at the ruffled borders, in-cell transportation, and evacuation from the apical membrane toward the extracellular). Although the role of osteoclasts in the metabolism of organic components is well documented, knowledge of the role of osteoclasts in the entire process of metabolism of Ca in bone has been fragmentary because no one has succeeded in directly observing such Ca in osteoclasts. Blood vessels actively absorb Ca released from bone by osteoclasts. Three hypothetical pathways for this uptake of Ca have been propose : (i)directly from resorption lacunae (i.e.the direct resorption pathway) ; (ii)through the intermediary of osteoclasts via Ca-specific channels (i.e.the channel-mediated transport pathway) ; (iii)through the intermediary of osteoclasts via transcytosis (i.e.the transcytosis transport pathway), which is analogous to the pathway for organic components. Although there is yet no evidence that definitively identifies any of these pathways or that refutes the transcytosis pathway, many researchers currently believe that the direct pathway is the main mechanism and that the channel-mediated pathway is a secondary mechanism. Among the three pathways, the transcytosis pathway seems to be least favored, only because no one has succeeded in directly observing Ca originating from bone in osteoclasts. To identify if the transcytosis pathway exists in osteoclasts, here we developed a method uses either fixed or living osteoclast-like cells (OCL) that were previously differentiated in vitro, uses a Ca-specific fluorescent dye (Fura Red^<TM>), to which a cell membrane is impermeable, and uses confocal laser scanning microscopy (LSM). We call this method the cell-membrane-impermeable dye (CMID) method. We used OCL because they are considered a good model of in vivo osteoclasts. Because the dye Fura Red^<TM> does not permeate an OCL membrane, the dye that exists inside OCL indicates active uptake, probably endocytosis, of the dye by OCL. If the Ca co-exists with such a dye inside OCL, direct and specific visualization of this Ca should be possible by detecting the emission from a dye-Ca complex. The Ca originating from bone might permeate OCL via two mechanisms : endocytosis and channels. If the quantity of such Ca is small (i.e.Ca via channels), the Ca would not be detectable, whereas if the quantity is large (i.e.Ca via endocytosis), it would be readily detectable and thus visualized. We therefore expected direct and specific visualization of the Ca via endocytosis by the CMID method. By using this method, we were successful in obtaining the first direct evidence that suggests massive Ca uptake occurs via endocytosis and that the Ca is transported toward the apical membrane side in OCL. This evidence also suggests that osteoclasts play an important role throughout the metabolism of Ca in bone.

  42. A study on mechanisms of tissue formation and regeneration of the dentin-pulp complex

    YOSHIBA Kunihiko, YOSHIBA Nagako, HOSOYA Akihiro, OZAWA Hidehiro

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

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

    Institution: Niigata University

    2004 - 2005

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    This study aims to elucidate mechanisms of tissue formation and regeneration of the dentin-pulp complex. The results were as follows : 1. During mouse tooth development, the expression of an intermediate filament nestin was intense in differentiating odontoblasts, and became restricted to the secretory pole of functional odontoblasts, suggesting that nestin plays a role in terminal differentiation, especially in cell elongation and/or polarization of odontoblasts. 2. Distinct temporal and spatial expression patterns of TIMPs suggest divergent functions of these factors in incisor organogenesis. Intense expression of Timp-1 was detected in differentiating odontoblasts, while Timp-3 was expressed by subodontoblasts, suggesting their involvement in odontoblast differentiation. 3. The unerupted rat incisor was composed of osteodentin, with numerous cells present in the anterior apex. The osteodentin was immunopositive for osteocalcin, bone sialoprotein, and dentin sialoprotein, with an immunolocalization pattern similar to that of dentin. These results indicate that osteodentin in the rat incisor possesses a dentin-like characteristics. 4. We performed a histological and immunohistochemical evaluation of mineralized tissue induced by pulp transplantation into subcutaneous tissue. The results indicate that pulp cells are able to form hard tissue with bone- or cementum-like characteristics without dentin influence. Calcification may start in necrotic cells and matrix vesicles, followed by collagenous calcification. 5. Pulpal responses to GaAlAs laser irradiation were elucidated. The results indicated that the GaAlAs laser may induce the formation of tertiary dentin by influencing the secretory activity of odontoblasts. However, higher energies may cause irreversible changes to the pulp, often leading to the formation of an intrapulpal bone-like tissue.

  43. 再生骨および歯と受容者(recipient)組織間の特異的相互作用の解析

    小澤 英浩, 高橋 直之, 八巻 真理子, 細矢 明宏, 二宮 禎, 星 和人

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 萌芽研究

    Category: 萌芽研究

    Institution: 松本歯科大学

    2004 - 2005

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    1. In vitroにおける歯の再生研究 胎生13日マウス歯胚を取り出し、コラゲナーゼにより上皮と間葉を分離後、single-cell suspensionを作製し、再構築して培養を行った。しかしながら、歯胚の発育は認められず、分離方法および培養条件などの検討が必要であると思われた。 2. In vivoにおける硬組織再生とrecipientとの相互作用 歯髄の硬組織形成機構に関する研究 6週齢雄性Wistar系ラットの下顎切歯固有歯髄を分離し、同系ラットの頭部皮下に他家移植した。移植3、7、14日後に移植片を周囲組織とともに取り出し固定、脱灰後パラフィンに包埋し、オステオカルシン(OCN)、オステオポンチン(OPN)、骨シアロタンパク(BSP)、象牙質シアロタンパク(DSP)及び組織非特異的アルカリホスファターゼ(TNAP)の局在を、免疫組織化学的に検索した 移植3日後、歯髄組織辺縁部では典型的な象牙芽細胞は消失したが、歯髄全体に強い変性は見られなかった。7日後、歯髄組織辺縁より内側に向かって細胞を封入した硬組織が形成され、この硬組織の内側表面には卵円形の細胞が観察された。14日後、硬組織形成はさらに進み、移植歯髄のほぼ全体に石灰化が認められた。新生硬組織及びその周囲の細胞は、OCN、OPN及びBSP陽性反応を示したが、DSPについては陰性であった。TNAPは3日後では歯髄組織辺縁部で局在を示し、7日以降は硬組織の内側表面で強い局在が認められた。さらに、GFP発現ラットを用いた歯髄移植実験から、硬組織形成細胞は歯髄細胞由来であることが明らかとなった。したがって、歯髄は歯の環境を離れた後も硬組織誘導能を有し、骨様組織形成を行ったことから、歯の硬組織再生における歯髄の有用性が示唆された。

  44. The establishment of inducible osteocyte ablation mouse model to elucidate the mechanisms of maxillo-mandibular dysmorphia.

    HOSOYA Akihiro, TAKAHASHI Naoyuki, OZAWA Hidehiro, NAKAMICHI Yuko, MIZOGUCHI Toshihide

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

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

    Institution: Matsumoto Dental University

    2003 - 2004

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    In maxillo-mandibular growth and development, osteocytes absorb mechanical stress generated by muscle contraction and deform bone structure. Thus, osteocytes are thought to be mechanosensory cells that respond to mechanical stress by sending signals to other bone cells to initiate bone remodeling. However, it has been difficult to show that osteocytic lineage are involved in bone remodeling in vivo. In present study, to define the role of osteocytes in the control of bone remodeling, we have tried to generate an inducible osteocyte ablation mouse model. Precisely, transgenic mice have been generated with mouse dentin matrix protein-1 (dmp-l) promoter, which is used to drive expression of Fas fused to mutant estrogen receptor (Fas-ER^t). Dmp-1 is an osteocyte-specific gene, and is expressed only in differentiated osteocytes but not in osteoblasts. Cells expressing (Fas-ER^t) die of tamoxifen treatment, expression of Fas-ER^t in osteocytes should allow inducible ablation of differentiated osteocytes in vivo without affecting the precursor cells, osteoblasts. First, we generated fusion genes composed of various length of the mouse dmp-1promoter fused to GFP reporter gene. The dmp-1-GFP fusion genes were transfected into osteoblastic MC3T3-E1 cells and some stable transformants were obtained. The transformants were cultured for 30 days and GFP activity was measured every days. Osteocyte-specific enhancer activity was observed in region between -1200 and -800bp. Next, we constructed Flag-tagged Fas-ER^t fusion gene and transiently transfected the gene into MC3T3-E1 cells. We tried to induce apoptosis in Flag-Fas-ER^t expressing cells by addition of anti-Flag antibody and tamoxifen, but we were able to induce cell death in only 30% population of these cells. We have examined another system that is more effective than Fas-ER^t. We have considered to use diphtheria-toxin receptor or herpes simplex virus thymidine kinase for inducible cell ablation system.

  45. Analysis of molecular mechanisms in bone formation and regeneration

    OZAWA Hidehiro, KAWAKAMI Toshiyuki, TAKAHASHI Naoyuki, UDAGAWA Nobuyuki, KAWAGUCHI Hiroshi, HOSOYA Akihiro

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)

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

    Institution: Matsumoto Dental University

    2002 - 2004

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    I. Molecular mechanisms of calcification in bone matrix formation : To identify the factor induce formation of the nuclear, we make monoclonal anti-body using matrix vesicle isolated from MLO-A5 cell in culture and clarified that the antigen localizes among the fibrae in extracellular matrix. Moreover, to estimate the effects of Mg in bone calcification, we determined the bone qualities, especially mineralization in Mg deficient rat. Loss of Mg was increased the value of Ca and had irregular crystal of hydroxyapatite in the rat. These findings indicate that the loss of Mg inhibits the crystallization of hydroxyapatite in matrix vesicle. II. Coupling mechanisms of bone metabolism : Bone formation and bone resorption were promoted in osteoprotegerin (OPG)-deficient mice. Bisphosphonate, a potential inhibitor of bone resorption, reduced both bone formation and bone resorption. Bone formation induced by bone morphogenetic protein in OPG-deficient mice did not exhibit any difference from that in wild mice. These results suggest that coupling factors activated or released by osteoclasts may be involved in the subsequent bone formation. We investigated the mechanism of osteoclastogenesis induced by lipopolysaccharide and interleukin (IL)-1. These factors induced the expression of RANKL in osteoblastic cells through MyD 88 and Ca/PKC-MEK/ERK pathways. III. Bone regeneration and reconstruction model : The subcutaneously transplanted rat dental pulp formed mineralized hard tissue possessing bone- or cementum-like characteristics, suggesting that dental pulp possesses the ability to hard tissue formation by itself. Bone formation induced laser light irradiation was shown to be caused by the odontoblast activation and the inhibition of osteoclastic bone resorption. In the study of prostaglandin E EP4 receptor agonist, the gene expression existed in odontoblast, and the bone formation activity was resulted from the decrease of adipocyte and the increase of osteoblast in bone marrow.

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Teaching Experience 3

  1. 解剖学・口腔解剖学　北海道医療大学

  2. 発生学　北海道医療大学、松本歯科大学

  3. 組織学・口腔組織学　北海道医療大学、松本歯科大学