持续被动运动条件下骨关节炎软骨细胞Erk活性及增殖

Erk activation and proliferation in osteoarthritc chondrocytes after continuous passive motion

背景:目前临床上对持续被动运动是否可通过改善软骨细胞的增殖能力而改善骨关节炎病情研究报道较少。目的:分析持续被动运动对兔骨关节炎的治疗作用及相关机制。方法:36只新西兰大白兔随机分为3组,每组12只。对照组兔子仅手术切开关节囊而不损伤关节软骨;模型组和治疗组采用Hulth方法建立骨关节炎模型。治疗组兔子在后第1天即开始进行持续被动运动治疗,8 h/d,连续8周。ELISA方法检测关节液白细胞介素1和肿瘤坏死因子含量;RT-PCR方法检测软骨细胞Ⅱ型胶原表达情况;MTT方法检测软骨细胞增殖能力;Western blot方法检测软骨细胞Erk信号通路活化情况。结果与结论:(1)模型组关节液中白细胞介素1和肿瘤坏死因子α含量显著升高,软骨细胞Ⅱ型胶原的mR NA表达水平出现显著下调,给予持续被动运动治疗后,关节液中白细胞介素1和肿瘤坏死因子α含量显著降低(P<0.01),同时软骨细胞Ⅱ型胶原的m RNA表达水平出现显著上调(P<0.01);(2)模型组软骨细胞增殖能力显著降低,而治疗组软骨细胞增殖能力显著升高(P<0.01);(3)模型组软骨细胞Erk信号通路活化情况出现显著下调(P<0.01),给予持续被动运动治疗后软骨细胞Erk信号通路活化情况水平出现显著上调(P<0.01)。提示持续被动运动可通过影响关节液中白细胞介素1和肿瘤坏死因子α水平、软骨细胞Ⅱ型胶原表达情况及软骨细胞增殖能力而改善骨关节炎病情,其机制可能与调节Erk信号通路活化情况相关。

BACKGROUND：Whether continuous passive motion improves osteoarthritis by enhancing the proliferation ability of chondrocytes is rarely reported. OBJECTIVE：To analyze the therapeutic outcomes of continuous passive motion in rabbits with osteoarthritis and the underlying mechanism. METHODS：Thirty-six New Zealand white rabbits were randomly al otted into three groups （n=12 per group）. Rabbits in control group only underwent capsulotomy with no harm to the cartilage;osteoarthritis models were established in the rabbits of model and treatment groups using Hulth method. At 1 day after modeling, the treatment group rabbits were treated with continuous passive motion, 8 hours daily for consecutive 8 weeks. Interleukin-1 and tumor necrosis factorαlevels in the synovial fluid were detected by ELISA;col agen type II expression and the proliferation ability of chondrocytes were detected by MTT assay;Erk signaling pathway activation was determined using western blot assay. RESULTS AND CONCLUSION：In the model group, interleukin-1 and tumor necrosis factorαlevels in the synovial fluid were significantly increased, and the expression level of col agen type II mRNA was remarkablely down-regulated. Continuous passive motion significantly downregulated interleukin-1 and tumor necrosis factorαlevels and up-regulated the col agen type II mRNA level （P〈0.01）. The model group showed significantly decreased proliferation ability of chondrocytes and down-regulated Erk signaling pathway activation, while after continuous passive motion, al above indicators were significantly improved （P〈0.01）. These results indicate that the continuous passive motion can al eviate osteoarthritis probably by influencing interleukin-1 and tumor necrosis factorαlevels, proliferation ability of chondrocytes, and col agen type II expression, as wel as regulating Erk signaling pathway activation.