初级纤毛信号转运对TMJ-OA软骨细胞分化的影响

软骨细胞分化异常是引起颞下颌关节骨关节炎（TMJ-OA）病理改变的重要因素，导致关节弹响、疼痛及运动受限。初级纤毛是具有调控细胞分化能力的细胞器，其功能受到纤毛信号转运蛋白的调节。申请人前期研究发现：纤毛信号转运蛋白IFT140参与髁突软骨的发育，促进髁突软骨细胞分化，缺失后引起髁突软骨发生骨关节炎样改变。据此，申请人首次提出IFT140是调节TMJ-OA软骨细胞分化的重要因子。在前期基础上，本项目将通过单侧咬合紊乱TMJ-OA模型、软骨细胞特异性敲除IFT140模型，细胞谱系示踪技术，转录组测序技术，探讨：1）IFT140在髁突软骨细胞时空表达特点；2）TMJ-OA中IFT140对软骨细胞分化功能的影响；3）IFT140影响软骨细胞分化的分子机制。本课题有望揭示初级纤毛是TMJ-OA软骨细胞退变的重要因素，为骨关节炎软骨结构和功能恢复提供理论依据。

The abnormal differentiation of chondrocytes is a key factor for TMJ-OA, resulting in joint snapping, pain and disability. Primary cilia have a role in regulating chondrocyte differentiation, and their functional integrity is regulated by Intraflagellar transport proteins. Our previous data show that IFT140 express in the condylar cartilage and have a role in promoting the differentiation of chondrocytes. Osteoarthritic changes of condylar cartilage were caused by the absence of IFT140. Accordingly, the applicant firstly proposed that IFT140 is a significant protein for the differentiation of chondrocytes in TMJ-OA and tissue repair. Based on these experiments, we established unilateral bite model and chondrocyte specific knockout of IFT140 model. Combining cell lineage tracing, this project aimed to investigate: 1)the persistent and instant expression of IFT140 in condylar chondrocyte; 2) functional verification of IFT140 in chondrocytes in TMJ-OA; 3) the role and mechanism of IFT140 in the differentiation of chondrocytes. This study will reveal the important source of chondrocyte regression in TMJ-OA and provide theoretical basis for tissue repair of osteoarthritis.