Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China.
Cell Signal. 2019 Nov;63:109379. doi: 10.1016/j.cellsig.2019.109379. Epub 2019 Jul 31.
Osteoarthritis (OA) is a highly prevalent skeletal disease. Mesenchymal stem cell-derived cartilage tissue engineering is a clinical method used for OA treatment. Investigations on the molecular regulatory mechanisms of the chondrogenic differentiation of synovium-derived mesenchymal stem cells(SMSCs) will help promote its clinical applications. In this study, bioinformatics analysis from three different databases indicated that the long non-coding RNA (lncRNA) MEG3 may regulate the chondrogenic differentiation of SMSCs by targeting TRIB2. We then performed assays and found that both knockdown of MEG3 or overexpression of TRIB2 can stimulate the chondrogenic differentiation of SMSCs and increase Col2A1 and aggrecan expression. Knockdown of MEG3 can induce the expression of TRIB2; conversely, overexpression of MEG3 can inhibit the expression of TRIB2. Futhermore, knockdown of the TRIB2 can rescue the MEG3 silencing-mediated promotion of chondrogenic differentiation. Moreover, RNA immunoprecipitation(RIP) and RNA pull-down assays demonstrated that MEG3 can interact with EZH2, thus recruiting it to induce H3K27me3, which promotes the methylation of TRIB2 by binding with the promoter of TRIB2 in SMSCs. Additionally, EZH2 silencing significantly rescued the MEG3 overexpression-mediated inhibition of TRIB2 expression and chondrogenic differentiation of SMSCs. Taken together, these data indicated that MEG3 regulates chondrogenic differentiation by inhibiting TRIB2 expression through EZH2-mediated H3K27me3.
骨关节炎（OA）是一种高发的骨骼疾病。间充质干细胞衍生的软骨组织工程是一种用于 OA 治疗的临床方法。研究滑膜间充质干细胞（SMSCs）软骨分化的分子调控机制将有助于促进其临床应用。在这项研究中，三个不同数据库的生物信息学分析表明，长链非编码 RNA（lncRNA）MEG3 可能通过靶向 TRIB2 来调节 SMSCs 的软骨分化。我们随后进行了实验，发现敲低 MEG3 或过表达 TRIB2 都可以刺激 SMSCs 的软骨分化，并增加 Col2A1 和聚集蛋白聚糖的表达。敲低 MEG3 可以诱导 TRIB2 的表达；相反，过表达 MEG3 可以抑制 TRIB2 的表达。此外，敲低 TRIB2 可以挽救 MEG3 沉默介导的促进软骨分化作用。此外，RNA 免疫沉淀（RIP）和 RNA 下拉实验表明，MEG3 可以与 EZH2 相互作用，从而招募它诱导 H3K27me3，通过与 SMSCs 中 TRIB2 的启动子结合，促进 TRIB2 的甲基化。此外，沉默 EZH2 可显著挽救 MEG3 过表达介导的 TRIB2 表达和 SMSCs 软骨分化抑制作用。综上所述，这些数据表明，MEG3 通过 EZH2 介导的 H3K27me3 抑制 TRIB2 的表达来调节软骨分化。
