| Project/Area Number |
18590359
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | National Institute for Longevity Sciences,NCGG |
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Principal Investigator |
TAKESHITA Sunao National Institute for Longevity Sciences,NCGG, National Center for Geriatrics and Gerontology, Dept of Bone and Joint Disease, Chief (50263009)
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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 |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Bone metabolism / Osteoporosis / Bone resorption / Bone formation |
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| Research Abstract |
A local 'coupling factor' linking bone resorption to subsequent formation has long been proposed as the key regulator for the bone remodeling process, but never identified. There are evidences in support of the view that osteoclasts regulate bone formation, We hypothesize that active osteoclasts resorbing bone produce 'coupling factors' which stimulate osteoblasts or bone formation. In order to identify such coupling factors as potent therapeutic drugs for osteoporosis, we performed DNA microarray analysis using 4 different RNAs ; bone marrow macrophages, preosteoclasts, inactive mature osteoclasts and active mature osteoclasts. We found a novel collagen domain-containing gene which was up-regulated in active mature osteoclasts. When this gene was retrovirally expressed in osteoblasts, stronger ALP staining was observed as compared to control. Recombinant protein was made by using a Baculovirus expression system and this also induced osteoblastogeneis of stromal cell line ST2. To elucidate the physiological function of this protein, transgenic mice and osteoclast-specific knockout mice were made. So far, Tg and KO mice seem to be high and low bone mass phenotypes, respectively, Further characterization of them as a coupling factor is under investigation.
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