软骨细胞分化是骨骼发育过程中的重要步骤，并且在骨关节炎发生过程中也具有重要作用。然而目前对软骨细胞分化及其在骨关节炎发生发展过程中的具体分子机制尚不完全清楚。近年研究发现Lis1蛋白在信号传导、细胞分裂和细胞运动等过程中发挥重要调控作用，但其在软骨细胞分化、骨骼发育及骨关节炎发生过程中的作用目前未有报道。我们的前期研究发现，在软骨细胞中特异性敲除Lis1基因显著抑制软骨细胞分化和骨骼发育，并且促进骨关节炎相关基因的表达。RNA-Seq发现在软骨前体细胞中敲除Lis1可导致细胞分裂、代谢、炎症等相关基因表达水平发生改变。本项目拟通过各种分子、细胞、动物模型及临床检测等手段，研究Lis1在软骨细胞分化和骨关节炎发生发展中的作用，阐明其可能的分子作用机制。本项目的开展有助于我们进一步了解关节炎的发病机制，为关节炎的治疗提供新的理论基础和潜在治疗靶点。

Chondrocyte differentiation plays critical roles in endochondral bone formation and Osteoarthritis (OA) pathogenesis. However, the molecular mechanism regulating chondrocyte hypertrophy during pathogenesis of OA remains poorly understood. Therefore, a more thorough investigation on the mechanism of how chondrocyte hypertrophy and OA progression are regulated is essential in order to develop better therapeutic treatments for patients. Recently, Lis1 was identified to control signaling transduction, cell mitosis, cell migration and so on. However, whether Lis1 regulates chondrocyte differentiation and cartilage homeostasis remains elusive. In our precious work, we found that deletion of Lis1 in cartilage inhibits chondrocyte maturation and endochondral bone formation. Besides, deletion of Lis1 in articular chondrocytes promotes OA-related genes expression. What’s more, RNA-Seq analysis showed that a series of genes related to cellular processed, metabolism and inflammation were affected by deletion of Lis1 in chondro-progenitor cells. In this project, surgical induced OA animal model, clinical testing, genetic modified mice and kinds of molecular cell biology technologies will be applied to study the function of Lis1 in the chondrocyte differentiation and progression of OA. This work will help us understand a more thorough molecular mechanism regulating the onsets, pathogenesis and progression of OA and provide a potential therapeutic target for treatment of OA.