大骨节病关节软骨细胞线粒体功能障碍，环境危险因素通过何种信号途径导致线粒体膜通透性转换孔（mPTP）开放的机制尚不清楚。基因表达谱分析发现大骨节病软骨细胞和外周血中p53通路显著高表达，免疫组化分析发现大骨节病深层软骨细胞中p53和CypD蛋白显著高于正常对照，p53-CypD通路对软骨细胞mPTP孔开放具有重要调控作用。本课题拟采用软骨细胞诱导和通路阻断等技术，重点研究p53-CypD通路对大骨节病软骨细胞mPTP孔的调控机制。首先检测大骨节病关节软骨组织和细胞中p53-CypD通路相关基因和蛋白表达特征；其次明确p53/ppif基因干扰对大骨节病软骨细胞mPTP孔开放的调控作用；最后明确环境危险因素通过p53-CypD通路诱导软骨细胞线粒体功能障碍。本项目将明确p53-CypD通路在大骨节病软骨细胞线粒体功能障碍中的作用，为明确大骨节病关节软骨损伤机制提供科学依据。

The articular chondrocytes of Kashin-Beck disease (KBD) occurred mitochondrial dysfunction, it is unclear that the signaling pathways induced by environmental risk factors result into mitochondrial permeability transition pore opening (mPTP). Gene expression profile analysis revealed significant higher expression of p53 pathway in chondrocytes and peripheral blood of KBD, and immunohistochemistry revealed significant higher expression of p53 and CypD proteins in deep chondrocytes of KBD, and the p53-CypD pathway played an important role in the mPTP opening of chondrocytes. In this study, chondrocyte induction and pathway blocking techniques were adopted to focus on the regulatory mechanism of p53-CypD pathway on mPTP pores of chondrocytes in KBD. Firstly, the p53-CypD pathway related with genes and proteins were detected in the articular chondrocytes and tissues of KBD. Secondly, the regulatory mechanism of p53/ppif gene interference on mPTP pore opening of chondrocytes in KBD. Finally, mitochondrial dysfunction of chondrocytes induced by environmental risk factors through the p53-CypD pathway. This project will clarify the mechanism of p53-CypD pathway in the mitochondrial dysfunction of chondrocytes in KBD, and provide scientific basis for clarifying the mechanism of cartilage damage in KBD.