软骨发育不良造成的骨骼发育异常可形成严重的青少年肢体畸形，除对症畸形矫治外，深入阐明软骨发育不良致病机制，选择靶向药物早期干预，可以有效地减轻畸形并延缓早发性骨性关节炎发生，编码细胞外基质蛋白的多种基因突变均可导致软骨发育不良的发生。研究表明突变基因引起软骨细胞基质蛋白分泌障碍及内质网应激反应是多种软骨发育不良的关键致病环节，课题组前期工作发现他汀类药物可以显著减轻EDM4型软骨发育不良小鼠软骨细胞内质网应激反应及肢体畸形，提示他汀类药物可能具有治疗软骨发育不良的潜在作用，但目前他汀类药物缓解软骨发育不良的分子机制及对其他类型软骨发育不良是否具有治疗作用尚不清楚。本项目拟采用多种软骨发育不良小鼠模型及软骨细胞体外培养相结合的方法，分别从体内疗效观察及体外分子机制探索两方面阐述他汀类药物治疗软骨发育不良的创新应用潜能，为将来儿童软骨发育不良及骨性关节炎的创新药物研制奠定重要理论基础。

The developmental defect of skeleton resulted from chondrodysplasia is the main reason of juvenile limb deformity in clinic. Besides of clinical deformity correction, the elucidation of chondrodysplasia pathogenesis and the specific intervention by target drug might effectively alleviate deformity and delay the beginning of secondary osteoarthritis. Many mutations within genes encoding cartilage extracellular matrix proteins have been demonstrated to induce chondrodysplasia, and these chondrodysplasias are featured by endoplasmic reticulum stress (ER stress) in chondrocytes due to the secretion defect of mutant matrix protein. Previous work by our team showed that Statins, compared to ER stress inhibitor, significantly alleviated ER stress and skeleton deformity of EDM4 type chondrodysplasia, indicating Statins might be a potential drug to treat chondrodysplasia. However, it remains unclear about the molecule target of Statins in this case and whether Statins could rescue other types of chondrodysplasia. By use of a few genetically manipulated mouse models of chondrodysplasia and in vitro chondrocytes culture together, this study plans to explore and elucidate the innovative potential of Statin in chondrodysplasia treatment through dissecting moue phenotype in vivo and investigating mechanism in vitro. This study will enrich our understanding on chondrodysplasia and have a theoretic significance to future innovative drug treatment of juvenile chondrodysplasia and osteoarthritis.