miR-877-5p alleviates chondrocyte dysfunction in osteoarthritis models via repressing FOXM1

Background The present study aimed to investigate whether forkhead box M1 (FOXM1), as a putative target of miR-877-5p, participated in interleukin (IL)-1 beta-induced cartilage degeneration in experimental osteoarthritis (OA) modelsin vitroandin vivo. Methods In vitroandin vivomodels of OA were established using IL-1 beta treated primary mouse chondrocytes and anterior cruciate ligament transection (ACLT) operation in mice. miR-877-5p mimics or agomir-miR-877-5p were used as therapeutic agents in bothin vitroandin vivomodels of OA. Cell viability and apoptosis were evaluated using cell counting kit-8 and terminal deoxynucleotidyl transferase dUTP nick end labeling staining, respectively. A quantitative reverse transcriptase-polymerase chain reaction and western blotting were used to measure gene and protein expression, respectively. Results FOXM1 was up-regulated in IL-1 beta-stimulated chondrocytes and the proximal tibia of ACLT-operated mice. Bioinformatics algorithms deduced a highly conserved sequence in the 3'-UTR of FOXM1 that could be bound with miR-877-5p. A luciferase assay indicated that miR-877-5p directly targeted the 3'-UTR of FOXM1. Overexpression of miR-877-5p could reduce protein expression of FOXM1 in chondrocytes. Concurrently, IL-1 beta-evoked up-regulation of FOXM1 protein expression was neutralized in chondrocytes following transfection with miR-877-5p mimics. miR-877-5p mimics or agomir-miR-887-5p could inhibit IL-1 beta-induced inflammation in bothin vitroandin vivomodels of OA. miR-877-5p might have beneficial effects on the synthesis of cartilage matrix via the promotion of SRY-box transcription factor 9 and type II collagen expression and inhibition of matrix metalloproteinase 9 expression. Conclusions miR-877-5p can improve chondrocyte function in bothin vivoandin vitromodels of OA, based on post-transcriptional repression of FOXM1 as a postulated molecular mechanism.