Department of Orthopaedics, Yangpu District Central Hospital affiliated to Tongji University School of Medicine, Shanghai 200090, China.
Department of Orthopaedics, Yangpu District Central Hospital affiliated to Tongji University School of Medicine, Shanghai 200090, China.
Bone. 2019 Jun;123:129-136. doi: 10.1016/j.bone.2019.03.035. Epub 2019 Mar 28.
MicroRNAs (miRNAs, miRs) are frequently dysregulated in osteoarthritis (OA), but the role of specific miRNAs in OA remains unclear. In this study, we found that miR-93-5p is underexpressed in human and rat OA-affected cartilage (compared with normal cartilage) as well as in IL-1β-treated chondrocytes. Overexpression of miR-93-5p promoted chondrocyte viability, suppressed chondrocyte apoptosis, and maintained the balance between anabolic and catabolic factors of the extracellular matrix in vitro. Similarly, injection of a miR-93-5p-expressing lentivirus alleviated the destruction of articular cartilage in a rat model of OA (anterior cruciate ligament transection). Furthermore, TCF4 was identified as a direct target gene of miR-93-5p. miR-93-5p directly targeted the 3' untranslated region (3'-UTR) of TCF4 mRNA and repressed TCF4 expression. Overexpression of TCF4 attenuated the effects of miR-93-5p on chondrocyte apoptosis and functions. Finally, analyses of miR-93-5p and TCF4 in OA-affected cartilage tissues revealed that miR-93-5p expression inversely correlated with TCF4 expression. Altogether, these findings indicate that miR-93-5p slows OA progression partially by suppressing TCF4 expression, and this phenomenon may provide novel insights into the function of miRNA in OA.
微小 RNA（miRNA，miRs）在骨关节炎（OA）中经常失调，但特定 miRNA 在 OA 中的作用尚不清楚。在本研究中，我们发现 miR-93-5p 在人及大鼠 OA 病变软骨（与正常软骨相比）以及 IL-1β 处理的软骨细胞中表达下调。miR-93-5p 的过表达促进软骨细胞活力，抑制软骨细胞凋亡，并维持细胞外基质合成代谢与分解代谢因子的平衡。同样，注射 miR-93-5p 表达的慢病毒可减轻大鼠 OA 模型（前交叉韧带切断）中关节软骨的破坏。此外，TCF4 被鉴定为 miR-93-5p 的直接靶基因。miR-93-5p 可直接靶向 TCF4 mRNA 的 3'非翻译区（3'-UTR）并抑制 TCF4 表达。TCF4 的过表达可减弱 miR-93-5p 对软骨细胞凋亡和功能的影响。最后，对 OA 病变软骨组织中的 miR-93-5p 和 TCF4 进行分析，结果显示 miR-93-5p 的表达与 TCF4 的表达呈负相关。综上所述，这些发现表明 miR-93-5p 通过抑制 TCF4 的表达来减缓 OA 的进展，这一现象可能为 miRNA 在 OA 中的功能提供新的见解。
