Periostin调控CD146+ADSCs软骨分化、胶原形成促进软骨界面整合及机制研究

关节软骨再生困难，良好的修复效果需要再生软骨与宿主软骨完好整合。我们在Wnt5a/软骨界面整合的研究中发现：Wnt5a促进ADSCs软骨分化基因表达，其下游Periostin基因表达也增加，沉默Wnt5a后Periostin基因表达显著下降；在软骨修复组织行基因和蛋白检测发现：整合良好的软骨界面处高表达Periostin和CD146，说明有CD146+亚型干细胞在界面处聚集，Periostin、CD146+ADSCs与软骨界面整合关系密切。本研究拟分选CD146+ADSCs，研究其增殖、凋亡、软骨分化及分子机制，构建Periostin基因修饰的CD146+ADSCs，评估其软骨分化和胶原形成能力；探讨Periostin与CD146作用机制，并通过异位及体内、外模型评估Periostin基因修饰的CD146+ADSCs/定向胶原在软骨修复和界面整合中的作用，为临床软骨修复提供理论基础。

Articular cartilage is difficult to regenerate when it was injured. Excellent repair effect requires a good integration of the regenerated cartilage with the host cartilage. In the study of Wnt5a/cartilage interface integration, we found that Wnt5a can promote chondrogenic differentiation gene expression of ADSCs, and its downstream Periostin gene expression also increased. After Wnt5a was silenced, Periostin expression decreased significantly. Further gene and protein detection in cartilage repair tissue in vivo showed that: Periostin, collagen and CD146 were highly expressed at cartilage interface with good regeneration and integration. It showed that CD146 positive stem cells gathered at the cartilage interface. Periostin, CD146+subtype ADSCs are closely related to the integration of cartilage interface. This study aims to sort CD146+ADSCs and evaluate their proliferation, apoptosis, cartilage differentiation, and molecular mechanisms; construct Periodin-modified CD146+ADSCs, and evaluate their cartilage differentiation and collagen-forming capabilities; explore the mechanism of Periostin and CD146. The role of Periostin genetically modified CD146+ADSCs/directional collagen in cartilage repair and interface integration will be assessed by ecpotic, in vitro and in vivo models.The results will provide theoretical and experimental basis for clinical cartilage repair.