首页> 中文期刊> 《实用医学杂志》 >T140体外阻断SDF-1/CXCR4信号通路阻止人关节软骨Ⅱ型胶原蛋白降解的研究

T140体外阻断SDF-1/CXCR4信号通路阻止人关节软骨Ⅱ型胶原蛋白降解的研究

         

摘要

Objective To explore the impact of blockade of SDF-1/CXCR4 signaling pathway by T140 on degradation of typeⅡ collagen in human articular cartilage and to define the mechanism of action of T140. Methods 144 pieces of cartilage (Mankin score of 0 or 1) were obtained from osteoarthritis patients undergoing total knee replacement ( OA cartilage group) and 144 pieces of cartilage (Mankin score of 0 or 1) were obtained from patients receiving traumatic amputation (normal cartilage group). Each group was treated with SDF-1 of 100 ng/mL, then divided into three subgroups A, B, and C. The cartilage tissue in each group was cultured in the nutrient solution containing of T140, MAB310, or SDF-1 (1 000 nmol/L) for 48 or 96 hours. RT-PCR was used to detect expression of typeⅡcollagen mRNA in the cartilage tissue. Results Level of type Ⅱcollagen mRNA was markedly higher in subgroup A than in subgroup B and subgroup C at the same group and the same time (P <0.05). The expression level of type Ⅱcollagen mRNA at the same time and in the same subgroup of OA cartilage group were lower than that in normal cartilage group (P < 0.05). Conclusions SDF-1 induces degradation of typeⅡcollagen in human articular cartilage thruogh the SDF-1/CXCR4 signaling pathway. T140 can block the SDF-1/CXCR4 signaling pathway and reduce the degradation of type II collagen.%目的:探讨T140体外阻断基质细胞衍生因子1(stromal cell derived factor 1,SDF-1)/趋化因子受体4(chemokine receptor 4,CXCR4)信号通路对人关节软骨细胞降解Ⅱ型胶原蛋白的影响,明确 T140的作用机制。方法:取144块膝关节置换OA患者软骨(OA软骨组)和144块创伤性截肢患者正常软骨(正常软骨组)组织,Mankin评分均为0或1,加入SDF-1(100 ng/mL)。每组再分为A、B、C三个亚组,分别加入浓度为1000 nmol/L 的 T140、MAB310和 SDF-1,分别于体外培养2、4 d 后,采用 RT-PCR 检测软骨组织Ⅱ型胶原蛋白mRNA表达。结果:相同软骨组在相同时间点,A组Ⅱ型胶原蛋白mRNA表达均显著高于B组和C组(P<0.05)。相同时间点,OA 软骨组同一亚组Ⅱ型胶原蛋白 mRNA 表达均显著低于正常软骨组(P<0.05)。结论:SDF-1通过 SDF-1/CXCR4信号通路诱导人关节软骨降解Ⅱ型胶原蛋白;T140阻断 SDF-1/CXCR4信号通路,缓解软骨细胞降解Ⅱ型胶原蛋白。

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