A therapy to eradicate osteoporosis

• Project/Area Number: 23590460
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Tottori University
• Principal Investigator: HAYASHI Shin-Ichi 鳥取大学, 医学部, 教授 (50208617)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 免疫学 / 骨吸収 / 炎症 / 病理学 / 再生医学 / 破骨細胞

Research Abstract

In this study, to develop the novel therapy for osteoporosis, regulatory cells for osteoclastogenesis were characterized. A removal of regulatory cells in peritoneal cavity resulted in the reduction of the osteoclatogenesis from bone marrow cells for more than 1 year. A removal of T lineage cells expressing CD4, CD8a, or CD5, but not B220, CD11b, CD11c, NK1.1, or IL7Ra in the bone marrow also reduced the osteoclastogenesis of bone marrow cells. These observations were confirmed by using mutant mice lacking T cells or T and B cells. Moreover, mice carrying T cell antigen receptor-transgene but not Btk mutation were affected a hypotonic treatment in the peritoneal cavity. Taken together, the osteoclastogenesis is suggested to be regulated by two-related systems presented in extra-medullary and intra-medullary sites.

Research Products

• [Journal Article] Dual system for the transport of self-antigens from the skin (2013)
  • Author(s): Yoshino, M., Murata, A., Shimoda, Y., Hikosaka, M., and Hayashi, S.I.
  • Journal Title: Curr. Res. in Immunology Volume: 7 Pages: 1-12
• [Journal Article] Dual system for the transport of self-antigens from the skin. (2013)
  • Author(s): Yoshino, M., Murata, A., Shimoda, Y., Hikosaka, M., and Hayashi, S.I.
  • Journal Title: Curr. Res. in Immunology, 7: 1-12 (2013). Volume: 7 Pages: 1-12
• [Journal Article] Origins and properties of dental, thymic, and bone marrow mesenchymal cells and their stem cells (2012)
  • Author(s): Komada Y, Yamane T, Kadota D, Isono K,Takakura N, Hayashi S, Yamazaki H
  • Journal Title: PLoS One Volume: 7(11) Issue: 11 Pages: e46436-e46436
  • DOI: 10.1371/journal.pone.0046436
  • Peer Reviewed
• [Journal Article] Stochastic differentiation into an osteoclast lineage from cloned macrophage-like cells (2012)
  • Author(s): Hayashi, S.I., Murata, A., Okuyama, K., Shimoda, Y., Hikosaka, M., Yasuda, H., and Yoshino, M.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 428 Issue: 2 Pages: 303-308
  • DOI: 10.1016/j.bbrc.2012.10.052
  • Peer Reviewed
• [Journal Article] CCR7-independent transport of skin antigens occurs in the dermis (2012)
  • Author(s): Yoshino, M., Okuyama, K., Murata, A., Tomura, M., and Hayashi, S.I.
  • Journal Title: Eur. J. Immunol. Volume: 42 Issue: 6 Pages: 1459-1467
  • DOI: 10.1002/eji.201142114
  • Peer Reviewed
• [Journal Article] A checkpoint in B-lymphopoiesis related to Notch resistance (2012)
  • Author(s): 奥山一生
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 417 Issue: 1 Pages: 141-146
  • DOI: 10.1016/j.bbrc.2011.11.072
  • Peer Reviewed
• [Journal Article] HLA-A2-restricted glypican-3 peptide-specific CTL clones induced by peptide vaccine show high avidity and antigen-specific killing activity against tumor cells (2011)
  • Author(s): Yoshikawa, T., Nakatsugawa, M., Suzuki, S., Shirakawa, H., Nobuoka, D., Sakemura, N., Motomura, Y., Tanaka-Harada, Y., Hayashi, S.I., and Nakatsura, T.
  • Journal Title: Cancer Sci. Volume: 102 Issue: 5 Pages: 918-925
  • DOI: 10.1111/j.1349-7006.2011.01896.x
  • NAID: 10029293106
  • Peer Reviewed
• [Journal Article] Methods for investigation of osteoclastogenesis using mouse embryonic stem cells (2011)
  • Author(s): Tsuneto M, Yamane T, Hayashi SI
  • Journal Title: Methods in Molecular Biology Volume: 690 Pages: 239-253
  • DOI: 10.1007/978-1-60761-962-8_16
  • ISBN: 9781607619611, 9781607619628
• [Presentation] Cell adhesion mediated by Notch ligands; an implication for mast cell accumulation in chronic inflammation (2013)
  • Author(s): Murata, A., Yoshino, M., Shimoda, Y., Hikosaka, M., Yagita, H., and Hayashi, S.I.
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 千葉(3-J-W56-12-P)
  • Year and Date: 2013-12-13
• [Presentation] Up-regulation of Aicda gene expression in IgE producing hybridomas : a model of class switch recombination in plasma cells (2013)
  • Author(s): Hikosaka, M., Murata, A., Shimoda, Y., Yoshino, M., and Hayashi, S.I.
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 千葉(2-H-W38-10-P)
  • Year and Date: 2013-12-12
• [Presentation] Analysis of cells transporting skin self-antigens to regional lymph nodes under CCR7-deficient conditions (2013)
  • Author(s): Yoshino, M., Murata, A., Shimoda, Y., Hikosaka, M., and Hayashi, S.I.
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 千葉(2-I-W39-19-P)
  • Year and Date: 2013-12-12
• [Presentation] Notch ligands differentially regulate the adhesion of immune cells (2012)
  • Author(s): Murata, A., Yoshino, M., Shimoda, Y., Hikosaka, M., Okuyama, K., Yagita, H., and Hayashi, S.I.
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸(2-D-W28-7-O/P)
  • Year and Date: 2012-12-06
• [Presentation] Role of CCR7-independent transport of skin self-antigens on skin immunity (2012)
  • Author(s): Yoshino, M., Okuyama, K., Murata, A., Tomura, M., Shimoda, Y., Hikosaka, M., and Hayashi, S.I.
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸(1-L-W21-3-O/P)
  • Year and Date: 2012-12-05
• [Presentation] Presence of CCR7-independent transport of skin antigens from the dermis (2012)
  • Author(s): Yoshino, M., Okuyama, K., Murata, A., Tomura, M., Shimoda, Y., Hikosaka, M., and Hayashi, S.I.
  • Organizer: European Congress of Immunology
  • Place of Presentation: Glasgow, Scotland
• [Presentation] CCR7-independent transport of skin antigens occurs in the dermis (2012)
  • Author(s): Yoshino, M., Okuyama, K., Murata, A., Tomura, M., Shimoda, Y., Hikosaka, M., and Hayashi, S.I.
  • Organizer: The 20th International Symposium on Molecular Cell Biology of Macrophages 2012
  • Place of Presentation: 東京
• [Presentation] CCR7-independent transport of skin antigens occurs in the dermis. (2012)
  • Author(s): Yoshino, M., Okuyama, K., Murata, A., Tomura, M., Shimoda, Y., Hikosaka, M., and Hayashi, S.I.
  • Organizer: The 20th International Symposium on Molecular Cell Biology of Macrophages 2012
  • Place of Presentation: 東京大学 （東京都文京区）
• [Presentation] Presence of CCR7-independent transport of skin antigens from the dermis. (2012)
  • Author(s): Yoshino, M., Okuyama, K., Murata, A., Tomura, M., Shimoda, Y., Hikosaka, M., and Hayashi, S.I.
  • Organizer: European Congress of Immunology,
  • Place of Presentation: Glasgow, Scotland, UK
• [Presentation] Role of CCR7-independent transport of skin self-antigens on skin immunity. (2012)
  • Author(s): Yoshino, M., Okuyama, K., Murata, A., Tomura, M., Shimoda, Y., Hikosaka, M., and Hayashi, S.I.
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸国際会議場（神戸）
• [Presentation] Notch ligands differentially regulate the adhesion of immune cells. (2012)
  • Author(s): Murata, A., Yoshino, M., Shimoda, Y., Hikosaka, M., Okuyama, K., Yagita, H., and Hayashi, S.I.
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸国際会議場（神戸）
• [Presentation] Characterization of CD16- NK cell precursors in the bone marrow (2011)
  • Author(s): Egawa, Y., Okuyama, K., Murata, A., Sawada, A., Shimoda, Y., Yoshino, M., and Hayashi, S.I.
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉(3-G-W58-3-O/P)
  • Year and Date: 2011-11-29
• [Presentation] Differential regulation of cell adhesion by Notch ligands (2011)
  • Author(s): Murata, A., Okuyama, K., Egawa, Y., Sawada, A., Shimoda, Y., Sakano, S., Yagita, H., Yoshino, M., and Hayashi, S.I.
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉(3-L-W68-15-P)
  • Year and Date: 2011-11-29
• [Presentation] No tch抵抗性を示すB細胞分化段階/Notch resistant checkpoint during B-lymphopoiesis (2011)
  • Author(s): Okuyama, K., Murata, A., Egawa, Y., Sawada, A., Shimoda, Y., Yoshino, M., and Hayashi, S.I.
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉(2-G-W37-9-P)
  • Year and Date: 2011-11-28
• [Presentation] Description of T cell receptor selection events with an in vitro culturing approach (2011)
  • Author(s): Sawada, A., Okuyama, K., Murata, A., Egawa, Y., Shimoda, Y., Yoshino, M., and Hayashi, S.I.
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉(1-L-W22-6-O/P)
  • Year and Date: 2011-11-27
• [Presentation] CCR7非依存的に皮膚自己抗原を輸送する担当細胞の探索/Analysis of cells transporting skin self-antigens to regional lymph nodes in a CCR7-independent manner (2011)
  • Author(s): Yoshino, M., Okuyama, K., Murata, A., Egawa, Y., Sawada, A., Shimoda, Y., and Hayashi, S.I.
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉(1-C-W4-11-P)
  • Year and Date: 2011-11-27
• [Presentation] Function of Notch ligands as adhesion molecules (2011)
  • Author(s): Murata, A., Okuyama, K., Egawa, Y., Sawada, A., Shimoda, Y., Yoshino, M., and Hayashi, S.I.
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 神奈川(4T11pII-2 (3P-0549))
• [Presentation] Presence of CCR7-independent transport of skin antigens from the dermis (2011)
  • Author(s): Yoshino, M., Okuyama, K., Murata, A., Egawa, Y., Sawada, A., Shimoda, Y., Hayashi, S.I.
  • Organizer: 76th Japanese Society of Interferon & Cytokine Research-19th International Symposium on Molecular Cell Biology of Macrophages 2011 Joint meeting
  • Place of Presentation: Osaka, Japan
• [Presentation] Function of Notch ligands as adhesion molecules. (2011)
  • Author(s): Murata, A., Okuyama, K., Egawa, Y., Sawada, A., Shimoda, Y., Yoshino, M., and Hayashi, S.I.
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜パシフィコ（神奈川）
• [Presentation] Characterization of CD16- NK cell precursors in the bone marrow. (2011)
  • Author(s): Egawa, Y., Okuyama, K., Murata, A., Sawada, A., Shimoda, Y., Yoshino, M., and Hayashi, S.I.
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] Differential regulation of cell adhesion by Notch ligands. (2011)
  • Author(s): Murata, A., Okuyama, K., Egawa, Y., Sawada, A., Shimoda, Y., Sakano, S., Yagita, H., Yoshino, M., and Hayashi, S.I.
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] No tch抵抗性を示すB細胞分化段階/Notch resistant checkpoint during B-lymphopoiesis. (2011)
  • Author(s): Okuyama, K., Murata, A., Egawa, Y., Sawada, A., Shimoda, Y., Yoshino, M., and Hayashi, S.I.
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] CCR7非依存的に皮膚自己抗原を輸送する担当細胞の探索/Analysis of cells transporting skin self-antigens to regional lymph nodes in a CCR7-independent manner. (2011)
  • Author(s): Yoshino, M., Okuyama, K., Murata, A., Egawa, Y., Sawada, A., Shimoda, Y., and Hayashi, S.I.
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] Description of T cell receptor selection events with an in vitro culturing approach. (2011)
  • Author(s): Sawada, A., Okuyama, K., Murata, A., Egawa, Y., Shimoda, Y., Yoshino, M., and Hayashi, S.I.
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] Up-regulation of Aicda gene expression in IgE producing hybridomas: a model of class switch recombination in plasma cells.
  • Author(s): Hikosaka, M., Murata, A., Shimoda, Y., Yoshino, M., and Hayashi, S.I.
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] Analysis of cells transporting skin self-antigens to regional lymph nodes under CCR7-deficient conditions.
  • Author(s): Yoshino, M., Murata, A., Shimoda, Y., Hikosaka, M., and Hayashi, S.I.
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] Cell adhesion mediated by Notch ligands; an implication for mast cell accumulation in chronic inflammation.
  • Author(s): Murata, A., Yoshino, M., Shimoda, Y., Hikosaka, M., Yagita, H., and Hayashi, S.I.
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Remarks]
  • URL: http://www.med.tottori-u.ac.jp/immunol/5983.html
• [Remarks] 鳥取大学医学部生命科学科分子細胞生物学講座免疫学分野
  • URL: http://www.med.tottori-u.ac.jp/immunol/5983.html
• [Remarks] 鳥取大学医学部生命科学科免疫学分野
  • URL: http://www.med.tottori-u.ac.jp/immunol/5983.html
• [Remarks]
  • URL: http://www.med.tottori-u.ac.jp/immunol/5983.html