| Project/Area Number |
10044246
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| Research Category |
Grant-in-Aid for Scientific Research (A).
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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 |
NODA Masaki Tokyo Medical and Dental University, Medical Research Institute, Professor, 難治疾患研究所, 教授 (50231725)
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| Co-Investigator(Kenkyū-buntansha) |
YAMASHITA Teruhito Tokyo Medical and Dental University, Medical Research Institute, Assistant Professor, 難治疾患研究所, 助手 (90302893)
NIFUJI Akira Tokyo Medical and Dental University, Medical Research Institute, Associate Professor, 難治疾患研究所, 助教授 (00240747)
DENHARDT Dav ラトガース大学, 生物学研究所, 教授
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥9,700,000 (Direct Cost: ¥9,700,000)
Fiscal Year 1999: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1998: ¥5,200,000 (Direct Cost: ¥5,200,000)
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| Keywords | osteopontin / knockout mouse / bone resorption / osteoclasts / bone formation / osteoblasts / osteoporosis / bone marrow ablatior / 老化 / エストロゲン / 病態生理学 |
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| Research Abstract |
Osteopontin is produced by osteoblasts and osteoclasts, is one of the more abundant non-collagenous proteins in bone matrix. However, the significance of the presence of osteopontin in in vivo has not been known. In our experiments, osteopontin-deficient and wild-type mice, 4.5-6 months old, were ovariectomized, while control animals were subjected to sham surgeries. We found that osteopontin knockout mice are resistant to ovariectomy-induced bone resorption compared to wild-type mice. Micro-computed tomography analysis indicated significant reduction in bone volume by ovariectomy in wild-type mice while the osteopontin-deficient mice exhibited less reduction in trabecular bone volume after ovariectomy. Histomorphometrical analysis of these trabecular bones confirmed the results of the μCT, demonstrating a large reduction in bone volume following ovariectomy in the wild-type mice, but only a slight, non-significant reduction in the osteopontin-deficient mice. Bone formation rate was increased following ovariectomy in wild-type animals, as expected, but was it not affected in osteopontin-deficient mice. The number of tartrate-resistant acid phosphatase (TRAP)-positive cells in the bones of wild-type animals was increased about three fold following ovariectomy, compared to sham-operated animals, while ovariectomy did not significantly increase the number of osteoclasts in osteopontin-deficient mice. Reduction in uterine weight was observed similarly in both wild-type and osteopontin-deficient mice indicating the specificity of the effect of osteopontin-deficiency on bone metabolism. We propose that osteopontin is essential for postmenopausal osteoporosis in women. Strategies to counteract osteopontin's action may prove effective in suppressing osteoporosis. These results confirm the resistance of the OPN-deficient mice to bone resorption following ovariectomy and established the importance of osteopontin in bone in osteoporosis and bone metabolism.
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