| Project/Area Number |
09307033
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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 | The University of Tokyo |
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Principal Investigator |
KAWAGUCHI Hiroshi Associate Professor, Graduate School of Medicine, The University of Tokyo, 医学部・附属病院, 講師 (40282660)
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| Co-Investigator(Kenkyū-buntansha) |
ODA Hiromi Associate Professor, Graduate School of Medicine, The University of Tokyo, 医学部・附属病院, 助教授 (60101698)
NAKAMURA Kozo Associate Professor, Graduate School of Medicine, The University of Tokyo, 医学部・附属病院, 教授 (60126133)
福井 尚志 東京大学, 医学部・附属病院, 助手 (10251258)
黒川 高秀 東京大学, 医学部・附属病院, 教授 (90010298)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥24,900,000 (Direct Cost: ¥24,900,000)
Fiscal Year 1999: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 1998: ¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 1997: ¥14,300,000 (Direct Cost: ¥14,300,000)
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| Keywords | fibroblast growth factor / fracture / primates / rheumatoid arthritis / bone formation / bone resorption / fibroblast growth factor / 成長因子 / 類人猿(サル) / 骨代謝 / サイトカイン |
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| Research Abstract |
One of the greatest needs in the bone field is a bioactive agent to stimulate bone formation. We previously reported that fibroblast growth factor-2 (FGF-2), a potent mitogen for a variety of mesenchymal cells, exhibited strong anabolic actions on bone formation in models of rodents and dogs. Aiming at a clinical application, here we report that a single local application of recombinant human FGF-2 exhibits strong osteogenic action in a fracture model of non-human primates. Although 4 out 10 animals treated with the vehicle alone remained in a nonunion state even after 10 weeks, bone union was complete at 6 weeks in all 10 animals treated with FGF-2. FGF-2 significantly increased bone mass and strength at the fracture site, and is therefore proposed to be an epochal bone anabolic agent for clinical use.
In addition, the effect of the synovial fluid from knee joints of rheumatoid arthritis (RA) patient with different severities of joint destruction on osteoclastogenesis and bone resorpti
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on was examined. The synovial fluid of RA patients with severe joint destruction significantly stimulated osteoclastic cell formation and ィイD145ィエD1Ca release from prelabelled cultured neonatal mouse calvariae, compared to those of RA patients with mild joint destruction and osteoarthritis (OA) patients. Among bone resorptive cytokines; FGF-2, tumor necrosis factor-a, interleukin-a, IL-6, and soluble IL-6 receptor, only FGF-2 concentration in the synovial fluid was positively correlated to Larsen's grade, and severe RA patients showed significantly higher FGF-2 concentrations than mild RA patients. Osteoclastogenesis in a co-culture system which was stimulated by the synovial fluid of severe RA patients was significantly inhibited by a neutralizing antibody against FGF-2 and this inhibition was stronger than antibodies against other cytokines. We conclude that the increase in endogenous FGF-2 production in the synovial fluid may play a role in the joint destruction of RA patients by inducing osteoclastogenesis. Less
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