基于IGF1R/PI3KCD通路ICS-HA通过miR-601调控软骨修复的分子机制研究

膝OA是中老年最主要致残性疾病，晚期发生不可逆畸形，故软骨早、中期修复为研究热点。前期研究发现，淫羊藿苷血清透明质酸水凝胶（ICS-HA）具有软骨早、中期细胞诱导和物理靶点修复作用及优势特性，但机制尚不清楚。预实验示ICS-HA通过miR-601及其下游靶基因IGF1R/PI3KCD抑制软骨退变。故本项目以ICS-HA促大鼠膝软骨早、中期修复为基础，以MSC与软骨细胞共浴体系模拟大鼠软骨细胞“微环境”，以软骨细胞增殖与功能表达为终点指标，通过①抑制/调高miR-601，调控IGF1R和PI3KCD的表达；②抑制/调高IGF1R和PI3KCD，调控终点指标的表达；③在体验证miR-601与IGF1R/PI3KCD调控作用及表达关系；④膝OA患者软骨标本中miR-601表达量与临床严重程度的相关性。确定ICS-HA软骨修复作用特性并阐明其作用分子机制，为临床膝OA的诊治提供定性思路和定量依据。

KOA is the most important disabled elderly diseases, and irreversible deformities occur in the late stage. Therefore, it is necessary to study early and mid-term cartilage repair. Previous studies have found that Hyaluronic acid combined icariin containing serum (ICS-HA) has the characteristics of early and middle cell induction and physical target repair in cartilage, but its mechanism is still unclear. Preliminary experiments showed that ICS-HA inhibited cartilage degeneration by regulating mir-601 and its downstream target gene IGF1R/PI3KCD. Therefore, this project was based on the promotion of early and intermediate repair of knee cartilage in rats by ICS-HA, and the co-bath system of MSC and chondrocytes was used to simulate the "microenvironment" of chondrocytes in rats,the proliferation and functional expression of chondrocytes were detected as an endpoint.① Mir-601 was inhibited/upregulated to regulate the expression of IGF1R and PI3KCD.② Inhibit/increase IGF1R and PI3KCD to regulate the expression of endpoint indicators;③ In the empirical evidence, mir-601 and IGF1R/PI3KCD regulated the cartilage repair effect and expression; ④ Clinical correlation expression of mir-601 in cartilage specimens of patients with KOA.Through these studies, the repair characteristics of ICS--HA cartilage were determined and the molecular mechanism of its action was elucidated, so as to provide qualitative thinking and quantitative evidence for the diagnosis and treatment of clinical KOA.