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《Chinese Journal of Sports Medicine》 2017-01
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The Influence of Blocking SDF-1/CXCR4 Signaling Pathway with TN14003 In Vitro on the Levels of Matrix Metalloproteinases 3,9 and 13 in Osteoarthritis Cartilages

Li Longteng;Li Yanlin;Wang Kun;Yan Xiangjia;Xiao Yu;Jia Di;Wang Guoliang;The First Affiliated Hospital of Kunming Medical University;  
Objective To explore the influence of blocking the stromal cells derived factor-1/CXCchemokine receptor 4(SDF-1/ CXCR4)signaling pathway using TN14003 on matrix metalloproteinases(MMP)3,9 and 13 levels secreted from osteoarthritis(OA)cartilages,so as to clarify the mechanism andeffect of TN14003. Methods Articular cartilage specimens were obtained from 6 OA patients duringthe total knee arthroplasty(n=6),cut into 140 explants of 3×3×3 mm3 and randomly divided into groupA,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 explantsin group D were incubated in the nutrient solution with SDF-1(100 ng/ml)only. The culture mediumwas collected on the end of the 2nd,4th,6th,8th and 10 th 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-9and MMP-13 of group A were significantly lower than group B,those of group B significantly lowerthan group C,which was significantly lower than group D. In the same group,the average levels ofMMP-3 and MMP-13 decreased(P0.05)gradually and that of MMP-9 increased gradually as(P0.05)the intervention went on. Conclusions TN14003,T140 and AMD3100 all can decrease the secretion ofMMP-3,MMP-9 and MMP-13 through blocking the SDF-1/CXCR4 signaling pathway,with TN14003 showing the best effect.
【Fund】: 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)
【CateGory Index】: R684.3
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