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.
Keywords: Apoptosis; Extracellular matrix; Osteoarthritis; TCF4; miR-93-5p.
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