| Project/Area Number |
10470302
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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 | The University of Tokyo |
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Principal Investigator |
NAKAMURA Kozo Graduate School of Medicine, The University of Tokyo, Professor, 医学部・附属病院, 教授 (60126133)
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| Co-Investigator(Kenkyū-buntansha) |
KAWAGUCHI Hiroshi Graduate School of Medicine, The University of Tokyo, Associate Professor, 医学部・附属病院, 講師 (40282660)
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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 |
¥8,700,000 (Direct Cost: ¥8,700,000)
Fiscal Year 1999: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 1998: ¥4,500,000 (Direct Cost: ¥4,500,000)
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| Keywords | fibroblast growth factor / osteoclast / bone resorption / MAP kinase / fibroblast growth factor -2 / 成長因子 |
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| Research Abstract |
Fibroblast growth factor-2 (FGF-2) at high and pharmacological concentrations is known to act on osteoblastic cells to indirectly stimulate osteoclastic bone resorption. In this study, we investigated the direct action of FGF-2 on mature osteoclasts using rabbit and mouse osteoclast cultures. FGF-2 (【greater than or equal】10-ィイD1-12ィエD1 M) exhibited stimulation on pit formation resorbed by isolated rabbit osteclasts with a maximum effect of 1.9-fold at 10ィイD1-11ィエD1 M and no further stimulation at higher concentrations, whereas FGF-2(【greater than or equal】10ィイD1-9ィエD1 M) showed stimulation on pit formation resorbed by unfractionated bone cells up to 7.5-fold. FGF-2 (【greater than or equal】10ィイD1-12ィエD1 M) also increased cathepsin K and MMP19 mRNA levels in mouse osteoclasts isolated from the co-culture of marrow cells and osteoblasts. Among FGF receptors (FGFR1 to 4), only FGFR1 was detected on isolated mouse osteoclasts, while all FGFRs were identified on mouse osteoblasts. FGF-2 (10ィイD1-12ィエD1 M) up-regulated the phosphorylation of cellular proteins including p42/p44 mitogen-activated protein (MAP) kinase, and increased the kinase activity of immunoprecipitated FGFR1 in mouse osteoclasts. The stimulation of FGF-2 on rabbit and mouse osteoclast functions was abrogated by PD98059, a specific inhibitor of p42/p44 MAP kinase. These results strongly suggest that FGF-2 acts directly on mature osteoclasts through activation of FGFR1 and p42/p44 MAP kinase, causing the stimulation of bone resorption at physiological or pathological concentrations.
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