circPhc3 sponging microRNA-93-3p is involved in the regulation of chondrocyte function by mechanical instability in osteoarthritis

Cartilage extracellular matrix (ECM) metabolism disorder caused by mechanical instability is a leading cause of osteoarthritis (OA), but the exact mechanisms have not been fully elucidated. Recent studies have suggested an important role of circular RNAs (circRNAs/circs) in OA. The present study aimed to investigate whether circRNAs might have a role in mechanical instability-regulated chondrocyte matrix metabolism in OA. The expression levels of circPhc3 in human and mouse OA cartilage samples were measured using reverse transcription-quantitative PCR and fluorescence in situ hybridization. The effects of circPhc3 on chondrocyte ECM metabolism were further investigated by overexpressing and knocking down circPhc3 in OA chondrocytes. The downstream target of circPhc3 was examined by performing a luciferase reporter assay. The results showed that the expression of circPhc3 was reduced in human and mouse OA cartilage. Moreover, circPhc3 was involved in mechanical loading-regulated production of ECM and cartilage-degrading enzymes. Further studies showed that circPhc3 regulated chondrocyte matrix metabolism primarily by binding to microRNA (miR)-93-3p, and mechanistic studies found that miR-93-3p targeting of FoxO1 was involved in chondrocyte matrix metabolism. Taken together, these results indicated that circPhc3 may serve an important role in the progression of OA and may be a good target for the treatment of OA.