瘦素在肿瘤坏死因子-α介导的软骨细胞死亡中的效应

Effects of Leptin on TNF-α-induced articular chondrocyte death

目的明确瘦素对肿瘤坏死因子-α(TNF-α)介导的软骨细胞死亡是否具有保护作用。方法从大鼠膝关节中分离关节软骨细胞后,采用TNF-α诱导软骨细胞死亡。将细胞采用瘦素处理3 h后采用TNF-α诱导细胞死亡。采用流式细胞术、细胞形态观察、凋亡及坏死蛋白水平检测及荧光染色分析细胞死亡。结果瘦素对TNF-α诱导细胞死亡具有保护作用,其能够通过部分影响软骨细胞的死亡及坏死发挥保护效应。JNK信号通路对TNF-α大鼠关节软骨细胞死亡具有保护作用。结论瘦素对由机械负荷及不利应激导致的软骨细胞损伤具有保护作用,其可能作为一种保护剂在骨关节炎患者治疗中应用。

Objective The objective of this study was to examine whether leptin modulates TNF- α- induced articular chondrocyte death. Methods Primary rat articular chondrocytes were isolated from knee joint cartilage slices. To induce cell death,the chondrocytes were treated with TNF- α. To examine whether leptin modulates the extent of TNF- α- mediated chondrocyte death,the cells were pretreated with leptin for 3 h before TNF- α treatment followed by viability analysis. To examine the mechanism by which leptin modulates the extent of TNF- α- mediated chondrocyte death,we utilized mitochondrial membrane potential measurements,flow cytometry,nuclear morphology observation,coimmunoprecipitation,western blot analysis and confocal microscopy. Results We demonstrated that leptin suppresses TNF- α induced chondrocyte death. We further found that apoptosis partially contributes to TNF- α induced chondrocyte death while necroptosis primarily contributes toTNF- α induced chondrocyte death. In addition,we observed that leptin exerts anti- TNF- α toxicity via JNK in rat articular chondrocytes.Conclusion We suggest that the leptin present in the articular joint fluid protects articular chondrocytes against cumulative mechanical load and detrimental stresses. We can further hypothesize that leptin protects articular chondrocytes against destructive stimuli even in the joints of OA patients.