| Project/Area Number |
15591562
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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 |
Orthopaedic surgery
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| Research Institution | Yamagata University |
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Principal Investigator |
TAKAHASHI Masatoshi Yamagata University, School of Medicine, Associate Professor, 医学部, 助教授 (10236341)
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| Co-Investigator(Kenkyū-buntansha) |
OGINO Toshihiko Yamagata University, School of Medicine, Professor, 医学部, 教授 (60109436)
TAKAGI Michiaki Yamagata University, School of Medicine, Associate Professor, 医学部, 助教授 (40241707)
TSUCHIDA Hiroyuki Yamagata University, School of Medicine, Associate Professor, 医学部, 助教授 (40250922)
MURA Nariyuki Yamagata University, School of Medicine, Assistant Professor, 医学部, 助手 (00312728)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | joint / digit / non-digit bearing / GDF5 / articular cartilage / gene therapy / brachypodism |
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| Research Abstract |
Growth/differentiation factor 5 (GDF5) is a member of the bone morphogenetic protein (BMP) family, which has been implicated in several skeletogenic events including cartilage and bone formation. We analyzed digit development in brachypodism (bp) mice, which carry functional null mutations of the Gdf5 gene. In situ detection of apoptosis and whole-mount detection of cell death showed abnormal apoptosis in the developing phalanges of bp mice. The condensed mesenchymal cells were progressively decreased in the developing phalanges and failed to form cartilage models of the middle phalanges. In addition, bp mice exhibited excessive apoptosis in the interdigital regions. These findings show that excessive apoptosis in the absence of GDF5 results in developmental failure of the phalanges. We conclude that GDF5 is essential for maintenance and growth of the developing phalanges.
We attempted regeneration of costal cartilage using human GDF5 proteins. However, GDF5 induced cartilage and bone in the injured sites. Bone was induced around the vascularized perichondrium, suggesting that vascularity was key for mesenchymal cells to differentiate osteoblasts or chondrocytes. GDF5 activates chondrogenesis and osteogenesis.
We analyzed the repair of full-thickness articular cartilage defect in the chick elbow joints. The repair of articular cartilage was poor in control group. There was no significant difference between control and GDF5-treated groups. Unfortunately, GDF5 could not have an effective role of joint regeneration even in non-weight bearing joints.
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