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

Abstract

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.

Keywords: FBXO21; autophagy; circRNA-MSR; miR-761; osteoarthritis.