T140体外阻断SDF-1/CXCR4信号通路对人关节软骨细胞分泌MMP-3、MMP-9和MMP-13水平的影响  

The Influence of Blocking SDF-1/CXCR4 Signaling Pathway with T140 on MMP-3,MMP-9,MMP-13 Level

作　　者：马珂[1] 李晓林 李彦林[3] 朱晓松[1] 王国梁[3] 赵沣凯 

机构地区：[1]昆明医科大学第一附属医院骨科,昆明650031 [2]楚雄州人民医院骨三科 [3]昆明医科大学第一附属医院运动医学科

出　　处：《中国运动医学杂志》2013年第9期807-810,823,共5页Chinese Journal of Sports Medicine

基　　金：国家自然科学基金资助项目(编号:30860286);云南省自然科学基金资助项目(联合专项)(编号:2010FB169)

摘　　要：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分泌基质金属蛋白酶(Matrix metalloproteinases,MMP)-3、MMP-9、MMP-13水平的影响,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天后,采用ELISA法测定培养液MMP-3、MMP-9、MMP-13含量,采用RT-PCR检测软骨组织MMP-3、MMP-9、MMP-13 mRNA表达。结果:相同软骨组在相同时间点,A组MMP-3、MMP-9、MMP-13含量及mRNA表达均显著低于B组和C组(P<0.05)。相同时间点,OA软骨组同一亚组MMP-3、MMP-9、MMP-13含量及mRNA表达均显著高于正常软骨组(P<0.05)。结论:SDF-1通过SDF-1/CXCR4信号通路诱导人关节软骨MMP-3、MMP-9、MMP-13表达和释放;T140阻断SDF-1/CXCR4信号通路,降低软骨细胞MMP-3、MMP-9、MMP-13 mRNA表达及分泌量。Objective To observed the influence of blocking SDF-1/CXCR4 signaling pathway on MMP-3,MMP-9,and MMP-13 levels in human articular cartilage ceils. Methods 144 cartilage pieces （Mankin score of 0 or 1）from patients with osteoarthritis （OA）（group OA）and 144 normal cartilage pieces（Mankin score of 0 or 1 ）（group C）were used in this study. After adding SDF-1 （10 ng/ml）,both groups were divided into three subgroups： experimental group （A）, experimental control group （B）, blank control group （C）. The cartilage tissue was cultured in the nutrient solution containing T140, MAB310, and SDF-1 （1000 nmol/L）for 48 or 96 hours. ELISA was used to measure the level of MMP-3, MMP-9,and MMP-13 in the culture medium; and RT-PCR was used to measure the expression of MMP-3, MMP-9, and MMP-13 mRNA in the cartilage tissue. Results The levels of MMP-3, MMP-9,and MMP- 13 ,and their expressions in group A were lower than in group B and C （P 〈 0.05）. The levels of MMP- 3 ,MMP-9,and MMP-13 ,and their expressions in subgroups of group AO were higher than group C（P 〈 0.05）. Conclusions T140 could block the SDF-1/CXCR4 signaling pathway and reduce the mRNA expression and secretion of MMP-3, MMP-9, MMP-13 in cartilage from patients with OA.

关 键 词：基质细胞衍生因子1 趋化因子受体4 金属基质蛋白酶 骨性关节炎 T140 

分 类 号：R684[医药卫生—骨科学]