摘要
目的:探讨TN14003体外阻断基质细胞衍生因子-1/趋化因子受体-4(SDF-1/CXCR4)信号通路对骨关节炎(osteoarthritis,OA)患者软骨组织分泌基质金属蛋白酶3、9、13(MMP-3、MMP-9、MMP-13)水平的影响,明确TN14003的作用机理和阻断效果。方法:对6例OA患者行膝关节置换术中采集透明软骨,切成3×3×3 mm3大小的软骨组织块(共140块),平均分为A、B、C、D四组进行体外培养,A、B、C三组分别加入TN14003、T140、AMD3100(使其在培养液中的最终浓度为1000 nmol/L),D组为空白对照组,四组培养液中均加入相同剂量SDF-1使其最终浓度为100 ng/ml,分别培养2、4、6、8、10天后取各组组织块培养液,采用ELISA检测培养液中MMP-3、MMP-9、MMP-13的含量。结果:相同时间点,MMP-3、MMP-9、MMP-13的分泌量A组低于B组(P<0.05),B组低于C组(P<0.05),C组低于D组(P<0.05);同一组内不同时间点,MMP-3、MMP-13的分泌量随时间而呈现总体降低趋势(P<0.05),MMP-9的分泌量随时间而呈现升高趋势(P<0.05)。结论:TN14003、T140、AMD3100均可阻断SDF-1/CXCR4信号通路,减低MMP-3、MMP-9、MMP-13的分泌,尤其以TN14003阻断效果最为确切。
Objective To explore the influence of blocking the stromal cells derived factor-1/CXC chemokine receptor 4（SDF-1/ CXCR4）signaling pathway using TNI4003 on matrix metalloproteinases （MMP）3,9 and 13 levels secreted from osteoarthritis（OA）cartilages,so as to clarify the mechanism and effect of TN14003. Methods Articular cartilage specimens were obtained from 60A patients during the total knee arthroplasty（n=6）,cut into 140 explants of 3×3×3 mm^3 and randomly divided into group A,B,C and D,each of 35. Explants in group A,B and C were incubated in the nutrient solution con- taining SDF-1（100 ng/ml）and TN14003,T140 and AMD3100（1000 nmol/L） respectively, while explants in group D were incubated in the nutrient solution with SDF-I（100 ng/ml）only. The culture medium was collected on the end of the 2nd,4th,6th,Sth and 10th day to measure the levels of MMP-3,MMP- 9 and MMP-13 using ELISA. Results At the same time points,the average levels of MMP-3,MMP-9 and MMP-13 of group A were significantly lower than group B, those of group B significantly lower than group C, which was significantly lower than group D. In the same group, the average levels of MMP-3 and MMP-13 decreased（P〈0.05）gradually and that of MMP-9 increased gradually as（P〈0.05） the intervention went on. Conclusions TN14003,T140 and AMD3100 all can decrease the secretion of MMP-3,MMP-9 and MMP-13 through blocking the SDF-1/CXCR4 signaling pathway,with TN14003 showing the best effect.
出处
《中国运动医学杂志》
CAS
CSCD
北大核心
2017年第1期44-47,共4页
Chinese Journal of Sports Medicine
基金
国家自然科学基金资助项目(编号81460340)
云南省创新团队项目(编号2014HC018)
云南省医疗卫生单位内设研究机构项目(编号2014NS161)
