CaR在TMJ骨关节炎关节软骨细胞异常增殖与分化中的作用研究

项目名称： CaR在TMJ骨关节炎关节软骨细胞异常增殖与分化中的作用研究

项目编号： No.81470762

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 王美青

作者单位： 中国人民解放军第四军医大学

项目金额： 100万元

中文摘要： 颞颌关节（TMJ）骨关节炎（OA）是临常见的颌面疾病，我课题组前期报道：异常咬合可致大鼠、小鼠TMJ出现OA样变，表现为软骨细胞终末分化、细胞凋亡、基质降解和细胞异常增殖。钙离子敏感受体CaR可促软骨细胞分化，在实验组TMJ软骨中，CaR先于胰岛素样生长因子-1（IGF-1）和甲状旁腺素相关蛋白（PTHrP）高表达，提示：CaR可能通过IGF-1信号和PTHrP信号，分别发挥促软骨细胞分化和增殖的作用。本项目拟对托马昔芬诱导的软骨特异性Car基因敲除鼠施以异常咬合，比较其TMJ 病变与野生鼠间，在软骨表型、PTHrP及IGF-1信号等方面的差别；离体培养髁突软骨细胞，分别施以钙刺激和力刺激，探讨CaR-IGF通路及CaR-PTHrP通路的活化特点；对咬合紊乱大鼠颞颌关节腔注射CaR抑制剂，观察对软骨退变的抑制效果。从而阐述CaR在促OA软骨细胞异常分化和异常增殖中的作用和靶向治疗意义。

中文关键词： 关节软骨；骨关节炎；颞下颌关节；咬合紊乱；钙离子敏感蛋白受体

英文摘要： Our previous data indicated that the abnormal dental occlusion induces osteoarthritis (OA)-like lesions in murine temporomandibular joint (TMJ) characterized by accelerated terminal differentiation, chondrocytes apoptosis, degradation of extracellular matrix, and aberrant cell proliferation. In the injured cartilage, CaR overexpression, which is known to promote chondroyte differentiation, is followed by up-regulation of IGF-1 and PTHrP, indicating that CaR might play an important role in chondrocytes differentiation and proliferation through IGF-1 and PTHrP signaling respectively. This project will induce abnormal dental occlusion in Tamoxifen inducible cartilage-specific Casr-KO (Tam-Casr-KO) mice and observe the changes of cartilage phenotype, activation of PTHrP and IGF-1 compared with that in wildtype mice. Chondrocytes isolated from SD rats will be treated with calcium ion and mechanical loading to conform the molecular mechanism in activation of CaR-IGF and CaR-PTHrP signaling. In addition, local injection of CaR inhibitor will be absorbed to demonstrate its inhibitive effect on cartilage degradation. The project aims to clarify the regulative role of CaR in abnormal chondrocytes differentiation and proliferation and its significance of targeted therapy in OA.

英文关键词： joint cartilage;osteoarthritis;temporomandibular joint;occlusion disorder;calcium-sensing receptor