miR-93-5p attenuates IL-1β-induced chondrocyte apoptosis and cartilage degradation in osteoarthritis partially by targeting TCF4.

Abstract

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.