滑膜间充质干细胞外泌体源性miR-376b-3p靶向MYC抑制骨关节炎进展  

Synovial mesenchymal stem cells exosomal derived miR-376b-3p inhibits osteoarthritis progression by targeting MYC

作　　者：牛学刚 刘朝旭 刘一帆[3] NIU Xuegang;LIU Zhaoxu;LIU Yifan(Bone Traumatology Department,Liaocheng Hospital of Traditional Chinese Medicine,Liaocheng 252000,China)

机构地区：[1]聊城市中医医院骨创伤科,聊城252000 [2]华中科技大学同济医学院附属同济医院骨科,武汉430030 [3]聊城市人民医院风湿免疫科,聊城252004

出　　处：《中国免疫学杂志》2022年第24期2945-2950,共6页Chinese Journal of Immunology

基　　金：国家自然科学基金项目(51877097)。

摘　　要：目的:探讨滑膜间充质干细胞(SMSCs)外泌体(exo)通过携带高水平的miR-376b-3p调控MYC对骨关节炎(OA)的作用。方法:IL-1β处理HC-A细胞建立OA损伤模型,分析miR-376b-3p、MYC水平变化。滑膜组织中分离SMSCs及exo,干预miR-376b-3p与MYC表达,CCK-8、流式细胞术和ELISA检测HC-A细胞增殖、凋亡、炎症因子IL-6、TNF-α分泌。结果:与对照组相比,OA组织与细胞中miR-376b-3p表达均下调(均P<0.05)。SMSCs源性exo能够促进软骨细胞增殖,抑制其凋亡,下调IL-6、TNF-α水平,该作用能被miR-376b-3p抑制剂部分抵消(均P<0.05)。MYC被证实是miR-376b-3p的靶基因且能促进OA软骨细胞损伤,对OA损伤的促进作用能被SMSCs源性exo部分抵消(均P<0.05)。结论:SMSCs源性exo携带的miR-376b-3p通过抑制MYC促进软骨细胞增殖,抑制其凋亡和炎症反应,从而抑制OA进展。Objective:To investigate effect of synovial mesenchymal stem cells(SMSCs)exosomes(exo)carrying high level of miR-376b-3p on osteoarthritis(OA)by regulating MYC.Methods:HC-A cells were treated by IL-1βto establish OA injury model,changes of miR-376b-3p and MYC levels were analyzed.SMSCs and exo were separated from synovial tissue,miR-376b-3p and MYC expressions were interfered,and proliferation,apoptosis and secretions of inflammatory factors IL-6,TNF-αof HC-A cells were detected by CCK-8,flow cytometry and ELISA.Results:Compared with control group,miR-376b-3p expression was down-regulated in OA tissue and cells(all P<0.05).SMSCs exo promoted chondrocyte proliferation,inhibited apoptosis,and down-regulated IL-6 and TNF-αlevels,which were partially rescued by miR-376b-3p inhibitor(all P<0.05).MYC was confirmed as a target gene of miR-376b-3p and promoted OA chondrocyte injury,whose effects on OA injury cells was partially saved by SMSCs exo(all P<0.05).Conclusion:SMSCs exo derived miR-376b-3p inhibit MYC to promote chondrocyte proliferation,inhibit apoptosis and inflammatory response,and subsequently inhibit OA progression.

关 键 词：滑膜间充质干细胞 外泌体 骨关节炎 miR-376b-3p 

分 类 号：R684.3[医药卫生—骨科学]