骨关节炎软骨细胞caveolin-1表达增高机制的探讨

目的 了解骨关节炎患者关节软骨内caveolin-1的表达情况,以及软骨降解因子自细胞介素(IL)-1β是否促进软骨细胞表达caveolin-1.方法 对8例骨关节炎患者膝关节软骨内caveolin-1基因表达的定量分析采用实时逆转录聚合酶链反应(RT-PCR),caveolin-1蛋白的表达采用免疫组化分析.选用12周龄的雄性SD大鼠20只,通过切断膝前交叉韧带和内侧副韧带制备骨关节炎模型,术后动态观察关节软骨的病理学变化和caveolin-1的表达情况.离体培养的骨关节炎软骨细胞内caveolin-1基因表达量分别采用RT-PCR和实时RT-PCR分析,caveolin-1蛋白表达量采用Western印迹分析.结果 与关节软骨轻微损害部位相比,8例骨关节炎患者中有6例患者的关节软骨严重损害部位内caveolin-1 mRNA表达增高约2倍,另外2例无明显差异.免疫组化分析显示,上述6例患者关节软骨严重损害部位内caveolin-1蛋白的表达也增高.随着术后时间延长,大鼠骨关节炎关节的软骨逐渐出现损害,且caveolin-1的表达也持续增高.IL-1β(10 ng/ml)可以上调培养的骨关节炎软骨细胞内caveolin-1基因和蛋白表达,并可持续至少48 h.结论 骨关节炎软骨损害程度与caveolin-1的表达水平具有相关性,IL-1β可以刺激软骨细胞表达caveolin-1.提示IL-1β可能通过诱导caveolin-1表达而促进骨关节炎进展.

Enhanced expression of caveolin-1 in articular chondrocytes in osteoarthritis

Objective To study the expression level of caveolin-1 in articular chondrocytes in patients with osteoarthrits(OA),and whether catabolic factor IL-1β stimulate caveolin-1 expression in articular chondrocytes. Methods In human OA cartilage, caveolin-1 mRNA wag investigated by quantitative real-time RT-PCR while caveolin-1 protein was detected by immuohistologic analysis in 8 cases OA model was prepared by unilatcral anterior cruciate ligament and medial collateral ligament transection in 20 rats.In cuItured OA chondrocytes,caveolin-1 mRNA expression was studied by RT-PCR and quantitative real-time RT-PCR,and caveolin-1 protein was analyzed by Western blouing.Results In 6 of 8 OA cases,human OA articular cartilage,higher expression levels of both caveolin-1 mRNA and caveolin-1 protein were found in advanced degenerated cartilage than less degenerated cartilage of the same joints.In rat OA model, uDregulated caveolin-1 expression wag found,which was associated with the degree of cartilage destruction.IL-1β(10 ng/ml)upregulated caveolin-1 mRNA/protein expression in cultured OA chondrocytes for at least 48 hours.Conclusion Enhanced expression level of caveolin-1 is associated with cartilage degeneration in OA.IL-1β stimulates caveolin-1 expression in articular chondrocytes,which may be responsible for OA development.