2007 Fiscal Year Final Research Report Summary
Transcriptional regulation of osteoclastogenesis
| Project/Area Number |
18390410
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
ASAGIRI Masataka Tokyo Medical and Dental University, Graduate School of Medicine, COE Research Associate Professor (Junior) (20372435)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Kojiro Saitama Medical University, Faculty of Medicine, Lecturer (10372434)
SHINOHARA Masayuki 東京医科歯科大学, 大学院・医歯学総合研究科, Research Associate (60345733)
TAKAYANAGI Hiroshi 東京医科歯科大学, 大学院・医歯学総合研究科, Professor (20334229)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Bone disease / Bone destruction / Rheumatoid arthritis / Periodontitis / Osteoclast / Transcription factor / Osteoporosis / Osteoimmunology |
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| Research Abstract |
Homeostasis of the skeletal system depends on a balance between bone-forming osteoblasts and bone-resorbing osteoclasts (Asagiri & Takayanagi, Bone 40 : 251-264, 2007). It has become increasingly clear that the excessive osteoclastic bone resorption relative to bone formation is highly associated with osteopenic diseases including osteoporosis and inflammatory bone diseases such as rheumatoid arthritis and periodontitis. Therefore, clarifying the mechanism(s) of differentiation and activation of osteoclasts is quite important from the clinical point of view. So far, we have already found that the expressions of some suppressive transcription factors are upregulated during osteoclastogenesis. Those include Pokemon/LRF/OCZF, a POK family protein that has both POZ/BTB domain and zinc fingers. In this study, our collaborators and we have made and analyzed transgenic mice that harbor additional Pokemon/LRF/OCZF gene under the control of cathepsin K promoter. Micro-CT, peripheral quantitativ
… More
e CT and histomorphometric analyses demonstrated a reduction in bone volume and bone mineral density in the transgenic mice. Histological analyses indicated an increase in the number of osteoclast, whereas bone formation rate did not significantly change. These results might suggest that Pokemon/LRF/OCZF has an important role in osteoclastogenesis in vivo (reported in ASBMR 29th Annual Meeting, 2007). In addition to that, we analyzed conditional knockout mice for Pokemon/LRF/OCZF gene (granted from professor Pandolfi of the Sloan-kettering Institute For Cancer Research). In terms of in vitro study, we retrovirally overexpressed Pokemon/LRF/OCZF in osteoclast precursor cells and analyzed the function. In total, both in vivo and in vitro studies have identified that the spatiotemporal control of Pokemon/LRF/OCZF expression is important for osteoclastogenesis and bone homeostasis. We further examined the transcriptome of inflammatory osteoclasts observed in rheumatoid arthritis (Asagiri et al., Science 319 : 624-7, 2008), however, a further study is necessary for molecular understanding of the roles of suppressive transcription factors in these cells. Less
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[Journal Article] Cathepsin K-Dependent Toll-like Receptor 9Signaling Revealed in Experimental Arthritis.2008
Author(s)
Asagiri M, Hirai T, Kunigami T, Kamano S, Gober HJ, Okamoto K, Nishikawa K, Latz E, Golenbock DT, Aoki K, Ohya K, Imai Y, Morishita Y, Miyazono K, Kato S, Saftig P, Takayanagi H.
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Journal Title
SCIENCE 319
Pages: 624-627
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Tyrosine kinases Btk and Tec regulate osteoclast differentiation by linking RANK and ITAM signals.2008
Author(s)
Shinohara M, Koga T, Okamoto K, Sakaguchi S, Arai K, Yasuda H, Takai T, Kodama T, Morio T, Geha RS, Kitamura D, Kurosaki T, Ellmeier W, Takayanagi H.
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Journal Title
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Cathepsin K-dependent Toll-like receptor 9 signaling revealed in experimental arthritis2008
Author(s)
Asagiri M, Hirai T, Kunigami T, Kamano S, Gober HJ, Okamoto K, Nishikawa K, Latz E, Golenbock DT, Aoki K, Ohya K, Imai Y, Morishita Y, Miyazono K, Kato S, Saftig P, Takayanagi H.
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Journal Title
SCIENCE Volume: 319 Issue: 5863
Pages: 624-627
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Tyrosine kinases Btk and Tec regulate osteoclast differentiation by linking RANK and ITAM signals2008
Author(s)
Shinohara M, Koga T, Okamoto K, Sakaguchi S, Arai K, Yasuda H, Takai T, Kodama T, Morio T, Geha RS, Kitamura D, Kurosaki T, Ellmeier W, Takayanagi H.
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Journal Title
CELL Volume: 132 Issue: 5
Pages: 794-806
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Estrogen prevents bone loss via estrogen receptor alpha and induction of Fasligand in osteoclasts.2007
Author(s)
Nakamura T, Imai Y, Matsumoto T, Sato S, Takeuchi K, Igarashi K, Harada Y, Azuma Y, Krust A, Yamamoto Y, Nishina H, Takeda S, Takayanagi H, Metzger D, Kanno J, Takaoka K, Martin TJ, Chambon P, Kato S.
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Journal Title
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts2007
Author(s)
Nakamura T, Imai Y, Matsumoto T, Sato S, Takeuchi K, Igarashi K, Harada Y, Azuma Y, Krust A, Yamamoto Y, Nishina H, Takeda S, Takayanagi H, Metzger D, Kanno J, Takaoka K, Martin TJ, Chambon P, Kato S.
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Journal Title
CELL Volume: 130 Issue: 5
Pages: 811-823
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Regulation of osteoclast differentiation and function by the CaMK-CREB Pathway.2006
Author(s)
Sato K, Suematsu A, Nakashima T, Takemoto-Kimura S, Aoki K, Morishita Y, Asahara H, Ohya K, Yamaguchi A, Takai T, Kodama T, Chatila TA, Bito H, Takayanagi H.
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Journal Title
NATURE MEDICINE 12
Pages: 1410-1416
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction.2006
Author(s)
Sato K, Suematsu A, Okamoto K, Yamaguchi A, Morishita Y, Kadono Y, Tanaka S, Kodama T, Akira S, Iwakura Y, Cua DJ, Takayanagi H.
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Journal Title
JOURNAL OF EXPERIMENTAL MEDICINE 203
Pages: 2673-2682
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Regulation of osteoclast differentiation and function by the CaMK-CREB pathway2006
Author(s)
Sato K, Suematsu A, Nakashima T, Takemoto-Kimura S, Aoki K, Morishita Y, Asahara H, Ohya K, Yamaguchi A, Takai T, Kodama T, Chatila TA, Bito H, Takayanagi H.
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Journal Title
NATURE MEDICINE Volume: 12 Issue: 12
Pages: 1410-1416
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction2006
Author(s)
Sato K, Suematsu A, Okamoto K, Yamaguchi A, Morishita Y, Kadono Y, Tanaka S, Kodama T, Akira S, Iwakura Y, Cua DJ, Takayanagi H.
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Journal Title
JOURNAL OF EXPERIMENTAL MEDICINE Volume: 203 Issue: 12
Pages: 2673-2682
Description
「研究成果報告書概要(欧文)」より
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