Myo6介导的囊泡转运与封闭区形成在破骨细胞分化与骨质侵蚀中的作用及其机制研究

类风湿关节炎（RA）的骨质侵蚀主要是由破骨细胞的过度活化引起的，而破骨细胞的骨吸收活性依赖于封闭吸收区的形成与基质酶的转运分泌，抑制破骨细胞的活性有可能成为 RA 治疗中保护骨质的可行方案。我们前期的研究发现， 肌球蛋白Myo6基因在破骨细胞分化过程中高表达，且随诱导时间而递增，同时与胶原诱导型关节炎小鼠骨质侵蚀呈正相关，提示Myo6可能参与了破骨细胞的分化与骨吸收过程。本项目将在前期研究基础上，利用基因干扰和过表达技术，从体外的细胞实验与体内的RA动物模型入手，系统探讨Myo6对破骨细胞封闭吸收区的形成与基质酶的转运分泌的调控机制，明确其在破骨细胞分化与骨吸收中的作用，以期为RA的治疗提供新的药物筛选靶点。

The bone erosion of Rheumatoid arthritis was mediated by over-activation of osteoclasts. Bone-resorbing osteoclasts are highly dependent on sealing zone formation and matrix enzyme trafficking and secretion. Therefore inhibition of osteoclast activity may be a protective therapeutic regimen for RA bone erosion. We found that the Myo6 gene was highly expressed during osteoclast differentiation in a time-dependent manner and had a positive correlation with the bone erosion of arthritis in our preliminary experiment, indicating Myo6 might participate in osteoclast differentiation and activation. In this project, we will explore the regulatory mechanism of Myo6 in osteoclast sealing zone formation and matrix enzyme trafficking and secretion in vivo cellular experiments and in vitro animal model of RA based on gene knockdown and overexpression technology; elucidate the important functions of Myo6 in the differentiation and activity of osteoclast. Our study will provide a new target of drug screening for RA treatment.