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Genes associated with cartilage differentiation and their application to cartilage repair

软骨分化相关基因及其在软骨修复中的应用

基本信息

批准号：
14370458
负责人：
KIMURA Tomoatsu
金额：
$ 9.09万
依托单位：
TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370458/
关键词：
cartilage repair gene collagen mesenchymal cell 転写因子

项目摘要

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.

目前的研究可以概括为三个类别：负责基因的分析，软骨分化和退化，识别候选蛋白/基因，结合到组织特异性元件的Col 11 a2基因，并修复软骨损伤，通过应用上述知识。首先，我们证明了EMSA中的几条带不与抗Sox 9抗体超移，但与Col 11 a2的软骨特异性增强子结合。我们用DNA亲和柱纯化了蛋白质，进行了LS-MS/MS分析，并鉴定了几个蛋白质/基因，这些蛋白质/基因正在进一步分析中。我们还发现了软骨中间层蛋白（CILP）基因作为软骨变性的易感基因（与池川博士合作，RIKEN）。我们证明CILP通过与TGFβ结合影响smad信号通路，调节软骨基质的合成，同时我们也证明了含有TGFβ家族的分化调节生长因子（CDMP 1/GDF 5）的工程化间充质细胞是一种上级的关节软骨修复细胞类型。将细胞移植或回输于关节软骨全层缺损和部分缺损处。这些细胞显著增强了软骨再生，并且缺损被透明软骨填充，软骨的更深表面区域被微结构重塑为正常软骨。