MCF2L基因在骨关节炎中的作用机制及功能研究

Osteoarthritis is a chronic, degenerative disorder of unknown cause. It is one of the most prevalent diseases in our society, with a worldwide distribution and high incidence and without racial and regional differences. Study for the etiology factor and pathological mechanism of osteoarthritis is a hotspot and focus. Our group has collected a number of osteoarthritis DNA sample and tissue samples with high quality and the susceptibility genes screening has been launched based on these samples. The results suggested that MCF2L gene is significant associated with the susceptibility of osteoarthritis in the Chinese Han population. More importantly, it is indicated that MCF2L may play roles in the proliferation of chondrocytes. Based on these findings, we plan to further clarify the effect and its underlying mechanism of MCF2L in the pathogenesis of osteoarthritis. Our study will provide theoretical basis and research foundation for genetic screening method, molecular etiology diagnosis and treatment on osteoarthritis.

骨关节炎(Osteoarthritis，OA)是一组原因不明的关节退行性疾病，该病在世界各地广泛分布，无明显种族和地域差异，且发病率高。对该病病因、病理机制的探索成为目前的热点和焦点。本课题组前期已收集了部分高质量的骨关节炎DNA样本及组织样本，正在以此为基础展开相关易感基因的筛查工作。前期结果首次确认了MCF2L基因与中国汉族人群骨关节炎发病的相关性，尤为重要的是， 我们还发现MCF2L基因的表达水平与软骨细胞的增殖密切相关，而软骨的退行性变化是骨关节炎病理进程的关键环节。本研究将从临床样本、软骨细胞及整体动物三个层面深入探讨MCF2L在骨关节炎发生、发展及治疗中的作用及相关机制，以期为应用遗传学方法筛查骨关节炎易感人群，分子病因学诊断及个体化治疗的可行性提供研究基础和理论依据。

骨关节炎是一组原因不明的关节退行性疾病，该病分布广泛，无明显种族和地域差异，发病率高且无有效治疗手段。因此，探索该病的病因及病理机制以期提出有效防治措施已成为当今的研究热点和焦点。本研究采集了大量高质量的骨关节炎DNA样本及组织样本，并首次证实了MCF2L基因多态性与中国汉族人群骨关节发病的遗传学相关性，且该基因在骨关节炎病人及骨关节炎小鼠模型软骨中表达均高于正常对照。在此基础上我们对MCF2L在骨关节中的作用机制展开了深入探讨，结果表明，作为Rho蛋白活性的重要调节分子，MCF2L可能通过调控RhoA/ROCK1及相应下游信号通路抑制软骨及软骨前体细胞分化、促进软骨及软骨前体细胞凋亡并抑制其增殖水平，从而在软骨发育及骨关节炎发生发展中发挥重要作用。本研究及后续工作的有序开展对进一步认识骨关节炎这一复杂疾病的分子机制、探寻骨关节炎的预防、早期诊断和个体化治疗方案提供了新的理论依据的和实验基础。