骨关节炎（OA）是一种常见关节退行性疾病，发病机理仍不十分明确。申请人研究发现：镁、骨桥蛋白（OPN）和软骨钙化与OA发生发展及疼痛症状密切相关，而镁与软骨钙化相关并可上调软骨细胞OPN表达。结合文献报道：镁可上调OPN表达从而抑制血管平滑肌细胞钙化，镁还可通过促进基质蛋白与整合素结合而调节其功能，提出假说：镁可调节软骨细胞OPN（一种基质蛋白）表达和功能，从而抑制软骨钙化，最终保护关节软骨并缓解疼痛症状。本项目拟采用siRNA干扰、基因过表达和CRISPR/Cas9基因编辑等技术，在体外细胞（单层和三维培养）与活体动物两个层面，明确镁和软骨钙化对OA发生发展及疼痛症状的影响，证实镁通过调节OPN表达和功能影响软骨钙化，并通过前瞻性队列研究进一步明确膝关节软骨钙化可促进人群膝OA发生发展并产生疼痛。从抑制软骨钙化的视角明确镁对OA的预防和治疗作用，为OA临床防治提供新思路。

Osteoarthritis (OA) is one of the most common diseases of aging people, the pathogenesis of which is still not very clear. Applicant’s study found that magnesium (Mg), osteopontin (OPN) and cartilage calcification are closely related to occurrence, development and pain symptoms of OA; Mg is related to cartilage calcification; Mg can promote the OPN expression in chondrocyte. Combined with literature reports, the up-regulated expression of OPN induced by Mg could inhibit calcification of vascular smooth muscle cells; Mg can modulate the function of matrix protein by promoting its binding with integrin. It could be speculated that Mg can promote the expression of OPN (a kind of matrix protein) in chondrocyte to inhibit cartilage calcification, thereby protect articular cartilage and alleviate pain symptoms. This project intends to elucidate the role of Mg and cartilage calcification in occurrence and development of OA and their influence on pain symptoms, to confirm that the inhibitory role of Mg in cartilage calcification is based on OPN, through both experiments of cells in vitro and animals in vivo using siRNA interference, gene overexpression and CRISPR/Cas9 gene editing technologies, and then perform a prospective cohort study to elucidate whether knee joint cartilage calcification can promote the occurrence, development and pain symptoms of knee OA in the general population, finally further confirm the prevention and treatment effect of Mg from the perspective of cartilage calcification and provide a new idea for the clinical prevention and treatment of OA.