Cx43半通道介导PGE2释放在异常咬合所致髁突软骨退变中的作用

项目名称： Cx43半通道介导PGE2释放在异常咬合所致髁突软骨退变中的作用

项目编号： No.81500896

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 张婧

作者单位： 中国人民解放军第四军医大学

项目金额： 20万元

中文摘要： 骨关节炎（OA）软骨退变的主要病理改变包括细胞过度死亡和软骨基质降解，常与异常生物力作用有关。我们前期临床研究结果显示，颞下颌关节（TMJ）OA与咬合异常密切相关，但异常咬合导致TMJ软骨退变的分子机理尚不清楚。最近我课题组通过建立大鼠和小鼠单侧前牙反合（UAC）模型，成功诱导出TMJ OA样变，并发现在UAC大鼠TMJ退变软骨的细胞中，力敏感性Cx43半通道蛋白表达水平明显增高，PGE2含量明显增加。PGE2是影响软骨细胞代谢活动的一种小分子量不饱和脂肪酸，可经Cx43半通道释放到细胞外，刺激软骨细胞分泌炎性因子和基质降解酶，导致软骨细胞凋亡、软骨基质降解、血管生成增多。本项目拟以Cx43基因敲除小鼠为研究对象，并结合软骨细胞体外加载实验，以期论证UAC异常咬合力致髁突软骨细胞Cx43半通道开放、PGE2释放增加，是其所致髁突软骨OA样变的重要分子病理机理，为OA防治提供新思路。

中文关键词： 颞下颌关节；骨关节炎；生物力；Cx43；PGE2

英文摘要： Abnormal mechanical loading can induce articular cartilage degeneration including chondrocytes apoptosis, extracellular matrix degradation and so on, which is one of the main pathologic changes of osteoarthritis (OA). Based on a large number of clinical studies, we found that TMJ OA is related to malocclusion, but the mechanism remains unclear. Recently, we established unilateral anterior crossbite (UAC) rat and mouse models which indeed causes OA-like changes in TMJ. We observed the expression of Cx43 protein, and the production and release of PGE2 all increased in mandibular condylar cartilage of UAC rats. PGE2 is unsaturated fatty acid with small molecular which can efflux through Cx43 hemichannels and promote chondrocytes apoptosis, extracellular matrix degradation, inflammation factors and matrix-degrading enzymes production, angiogenesis and so on. In this study, we will use the inducible Cx43 knockout mouse, and isolated TMJ chondrocytes with in vitro biomechanical loading combined, to claim that UAC abnormal bite force leads to the opening of Cx43 hemichannels and increased PGE2 release, revealing the mechanism of UAC induced mandibular cartilage degeneration. By the above exploration, a new target for OA treatment will be provided.

英文关键词： temporomandibular joint;osteoarthritis;biomechanic;Cx43;PGE2