circRNA‐MSR regulates the expression of FBXO21 to inhibit chondrocyte autophagy by targeting miR ‐761 in osteoarthritis

Osteoarthritis (OA) is a chronic degenerative joint disease and is the most prevalent and disabling form of arthritis worldwide. Autophagy plays a vital role in OA. This study aimed to explore whether covalently closed circular RNA MSR (circRNA‐MSR) could affect the F‐box Only Protein 21 (FBXO21) expression by targeting microRNA‐761 (miR‐761), thereby affecting the autophagy in OA chondrocytes. Clinical OA tissues were collected, and circRNA‐MSR, miR‐761, and FBXO21 expressions were detected via quantitative real‐time polymerase chain reaction (qRT‐PCR). An in vitro OA model was constructed by treating C28/I2 cells with LPS and treating them with overexpression or knockdown vector of circRNA‐MSR, miR‐761, and FBXO21, and autophagy inhibitor 3‐MA. Fluorescence in situ hybridization (FISH) determined the location of circRNA‐MSR and miR‐761. Dual‐luciferase assay assessed circRNA‐MSR and miR‐761, along with the bindings of miR‐761 and FBXO21. Cell viability was detected by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. LC3 II/I, p62 and beclin 1 expressions were detected via the western blot. circRNA‐MSR and FBXO21 levels were elevated in OA, but miR‐761 level was inhibited. Suppressing circRNA‐MSR promoted the autophagy of LPS‐treated cells. circRNA‐MSR could bind to miR‐761 and inhibit its expression. MiR‐761 inhibition reversed the promoted autophagy caused by circRNA‐MSR knockdown in LPS‐treated C28/I2 cells. Moreover, miR‐761 could target FBXO21 and inhibit its expression. FBXO21 overexpression reversed the increased autophagy caused by miR‐761 overexpression in LPS‐treated C28/I2 cells. circRNA‐MSR could affect FBXO21 level via targeting miR‐761, thereby repressing autophagy in OA chondrocytes, providing a new target and strategy for OA treatment.