Osteoarthritis (OA) is one of the most common diseases of the skeleton. Long non-coding RNAs (lncRNAs) are emerging as key players in OA pathogenesis. This work sets out to determine the function of lncRNA MALAT1 in OA and the mechanisms by which it does so. Mesenchymal stem cells isolated from the human synovial membrane are called hSMSCs. The hSMSCs’ surface markers were studied using flow cytometry. To determine whether or not hSMSC might differentiate, researchers used a number of different culture settings and labeling techniques. The expression levels of associated genes and proteins were determined using quantitative real-time polymerase chain reaction (RT-qPCR), western blotting (WB), and immunostaining. A dual luciferase reporter experiment and RNA immunoprecipitation (RIP) test demonstrated the direct association between miR-212-5p and MALAT1 or MyD88. MALAT1 was downregulated during the chondrogenic differentiation of hSMSCs, and underexpression of MALAT1 promotes chondrogenesis in hSMSCs. Using dual luciferase reporter and RIP assays facilitated the identification of MALAT1 as a competitive endogenous RNA (ceRNA) that sequesters miR-212-5p. Additionally, the expression of MYD88 was regulated by MALAT1 through direct binding with miR-212-5p. Significantly, the effects of MALAT1 on the chondrogenic differentiation of hSMSCs were counteracted by miR-212-5p/MYD88. Furthermore, our in vivo investigation revealed that the inhibition of MALAT1 mitigated osteoarthritis progression in rat models. In conclusion, the promotion of chondrogenic differentiation in hSMSCs and the protective effect on cartilage tissue in OA can be achieved by suppressing MALAT1, which regulates the miR-212-5p/MyD88 axis.

骨关节炎（OA）是最常见的骨骼疾病之一。长非编码 RNA (lncRNA) 正在成为 OA 发病机制的关键参与者。这项工作旨在确定 lncRNA MALAT1 在 OA 中的功能及其发挥作用的机制。从人类滑膜中分离出来的间充质干细胞被称为 hSMSC。使用流式细胞术研究 hSMSC 的表面标记。为了确定 hSMSC 是否可能分化，研究人员使用了多种不同的培养环境和标记技术。使用定量实时聚合酶链反应（RT-qPCR）、蛋白质印迹（WB）和免疫染色测定相关基因和蛋白质的表达水平。双荧光素酶报告基因实验和 RNA 免疫沉淀 (RIP) 测试证明 miR-212-5p 与 MALAT1 或 MyD88 之间存在直接关联。MALAT1在hSMSCs的软骨形成过程中下调，并且MALAT1的低表达促进hSMSCs的软骨形成。使用双荧光素酶报告基因和 RIP 检测有助于将 MALAT1 鉴定为隔离 miR-212-5p 的竞争性内源 RNA (ceRNA)。此外，MYD88 的表达受到 MALAT1 通过与 miR-212-5p 直接结合的调节。值得注意的是，MALAT1 对 hSMSC 软骨分化的影响被 miR-212-5p/MYD88 抵消。此外，我们的体内研究表明，抑制 MALAT1 可以减轻大鼠模型中骨关节炎的进展。总之，通过抑制调节miR-212-5p/MyD88轴的MALAT1可以实现促进hSMSCs软骨分化和对OA软骨组织的保护作用。