MicroRNA-671-3p regulates the development of knee osteoarthritis by targeting TRAF3 in chondrocytes

Abstract

Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation and joint inflammation. A previous study showed that microRNA (miR)-671-3p is involved in the development of OA, however, its function and molecular target in chondrocytes during the pathogenesis of OA remain to be fully elucidated. In the present study, miR-671-3p was significantly downregulated in knee OA cartilage tissues compared with normal cartilage tissues. The expression levels of pro-inflammatory cytokines, including interleukin (IL)-1β, IL- 6, IL- 8 and tumor necrosis factor (TNF)-α, in the knee OA cartilage tissues were significantly higher than those in the normal cartilage tissues. Through gain-of-function and loss-of-function experiments, miR-671-3p was shown to significantly affect matrix synthesis gene expression, cell proliferation, apoptosis and inflammation in chondrocytes from patients with OA. Subsequent bioinformatics analysis identified potential target sites of the miR-671-3p located in the 3'untranslated region of TNF receptor-associated factor (TRA F3). The results of a dual-luciferase reporter assay showed that TRA F3 is a target gene of miR- 671-3p. Western blot analysis demonstrated that miR- 671-3p inhibited the gene expression of TRA F3. Furthermore, the restoration of TRA F3 markedly abrogated the effect of miR- 671-3p. Taken together, the present study suggests that miR- 671-3p may be important in the pathogenesis of OA through targeting TRA F3 and regulating chondrocyte apoptosis and inflammation, which may be a potential molecular target for OA treatment.