透骨消痛胶囊通过激活CXCL12/GDF5通路修复骨关节炎小鼠的软骨损伤

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Abstract：ObjectiveToexplorethemechanismbywhichTougu Xiaotong Capsule （TXC）promoteschondrogenicdiferentiation andcartilagerepairinmicewithosteoarthritis（OA）MethodsFifty8-wee-oldmaleC57BLmicewererandomlydividedinto normalcontrolgroup，cartilagedamage （inducedbysubchondral ring-shapeddriling）modelgroupandTXCtreatment groupsat low， moderateand high doses （184，368 and 736mg/kg， respectively）. Saline （in normal control and model groups） andTXCwereadministeredaftermodelingbydailygavagefor6consecutiveweeks.Thechangesofcartilagedamageinthe mice were assessed bymeasuring thermal withdrawal latency （TWL）and mechanical withdrawal threshold （MWT）and using micro-CT，modifiedsafranineOandfastgreenstaining，HEstaining，andqPCR.Primaryculturesof mousesynovial mesenchymalstemcells （SMSCs）withlentivirusvectortransfectionforinterferingCXCL12，TXCtreatment，orboth for 24h wereexamiedforcodrogenicdiferetiationusingmunofluorescenceainingratchssyimunoctohstryd Western blotting.Results In mouse models withcartilage damage，TXCtreatmentatthe moderate dosesignificantlyalleviated joint pain，promotedcrtilagereirandureguatedtheRNAexpresio levelsofXC12，GDF5，collagen Igcan Comp and Sox9 in the cartilage tisse. In primary mouse SMSCs，CXCL12 knockdown resulted in significant reduction of GDF5 protein expression， migration abilityand Sox9 proteinexpresion，and these changes were obviouslyreversed by TXC treatment.ConclusionTXCpromoteschondrogenicdiferentiationof mouseSMSCstopromoterepairofcartilagedamagein mice by activating the CXCL12/GDF5 pathway.

Keywords： Tougu Xiaotong Capsule; synovial mesenchymal stem cells; cartilage damage; CXCL12/GDF5 pathway

软骨损伤是骨关节炎（OA）的关键病理表现之二[1，2]，由于关节软骨缺乏血管、神经及淋巴管等营养供给，其修复仍然是当前临床面临的重大难题3。（剩余14194字）