| 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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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥17,620,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥2,220,000)
Fiscal Year 2007: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Fiscal Year 2006: ¥8,000,000 (Direct Cost: ¥8,000,000)
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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
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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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