| Project/Area Number |
13470309
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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 | Osaka University |
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Principal Investigator |
NAKASE Takanobu Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (00283755)
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| Co-Investigator(Kenkyū-buntansha) |
MYOUI Akira Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (10263261)
HASHIMOTO Jun Osaka University Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (40237938)
YOSHIKAWA Hideki Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (60191558)
冨田 哲也 大阪大学, 医学系研究科, 助手 (30283766)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥10,400,000 (Direct Cost: ¥10,400,000)
Fiscal Year 2002: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2001: ¥6,400,000 (Direct Cost: ¥6,400,000)
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| Keywords | bone morphogenetic protein / spondylosis / fracture / gene expression / hedgehog protein / parathyroid hormone related protein / osteogenesis / chondrogenesis / 変形性関節症 / 軟骨細胞 / 免疫組織化学 / 内軟骨性骨化 / 脊椎症 |
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| Research Abstract |
Gene expression of bone morphogenetic protein (BMP) and osteochondrogenic factors related with BMP in various orthopaedic diseases was analyzed in this study.
1) Involvement of PTHrP and Ihh in the process of human endochondral ossification was indicated. 2) Stage and site specific gene expression of PTHrP and hedgehog protein in the process of experimental spondylosis was clarified. 3) Sonic hedgehog (Shh) is one of the major factors regulating BMP-4 function. Shh mRNA was up-regulated in the early phase post fracture as well as its signaling factor, Ptc. 4) Expression of BMP-2 in osteoarthritic cartilage was dependent of the severity of cartilage damage. BMP-2 was expressed in articular chondrocytes in response to the articular damage, and BMP-2 might become a marker indicating disease activities of osteoarthritis. These series of studies may clarify the target of molecular therapy of orthopaedic diseases.
Towards the development of a novel molecular-biology-based treatment method, a system of targeted expression of genes for BMP-4 and its antagonist noggin was developed using transgenic mice. Over-expression of BMP-4 gene lead to the enhanced formation of bone/cartilage. Over-expression of noggin gene lead to the inhibition of osteo- and chondro-genesis. This system may become a powerful tool for the development of successful and novel treatment to enhance bone/cartilage formation in vivo.
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