2004 Fiscal Year Final Research Report Summary
Genes associated with cartilage differentiation and their application to cartilage repair
| Project/Area Number |
14370458
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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 | TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
KIMURA Tomoatsu Toyama Medical & Pharmaceutical Univ., Dept. of Orthopaedics, Professor, 医学部, 教授 (80167379)
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| Co-Investigator(Kenkyū-buntansha) |
MORITA Yuji Toyama Medical & Pharmaceutical Univ., Dept. of Orthopaedics, Assistant Professor, 医学部, 助手 (30313604)
MATSUSHITA Isao Toyama Medical & Pharmaceutical Univ., Dept. of Orthopaedics, Assistant Professor, 医学部, 助手 (80345587)
WAKITANI Shigeyuki Shinshu Univ., Dept. of Orthopaedics, Associate Professor, 医学部, 講師 (70243243)
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| Project Period (FY) |
2002 – 2004
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| Keywords | cartilage / repair / gene / collagen / mesenchymal cell |
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| Research Abstract |
The present study can be summarized into three categories ; analysis of genes responsible for, cartilage differentiation and degeneration, identification of candidate proteins/genes that bind to the tissue-specific element of Col11a2 gene, and repair of cartilage damage by applying above knowledge. Firstly, we demonstrated several bands in EMSA that did not supershift with anti-Sox 9 antibody, but bind to cartilage-specific enhancer of Col11a2. We have purified the proteins by DNA affinity column, processed for LS-MS/MS analysis, and identifiend several proteins/genes which are now under further analysis. We also found cartilage intermediate layer protein (CILP) gene as a susceptibility gene for cartilage degeneration (in collaboration with Dr. Ikegawa, RIKEN). We demonstrated that CILP affects smad signaling by binding to TGFβ and regulates cartilage matrix synthesis.
We also demonstrated that engineered mesenchymal cell with differentiation regulating growth factor of the TGFβ family (CDMP1/GDF5) was a superior cell type for articular cartilage repair. The cells were transplanted or transfused into full-thickness articular cartilage defect as well as partial thickness defect. Cartilage regeneration was significantly enhanced with these cells and the defect was filled with hyaline cartilage, the deeper to surface zones of the cartilage being microstructurally remodeled to normal cartilage.
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Research Products
(14 results)
