Circular RNA Derived from Vacuolar ATPase Assembly Factor VMA21 Suppresses Lipopolysaccharide-Induced Apoptosis of Chondrocytes in Osteoarthritis (OA) by Decreasing Mature miR-103 Production.

Abstract

Circular RNA derived from vacuolar ATPase assembly factor (VMA21) has been proven to be an inflammation suppressor in many diseases, while its role in osteoarthritis (OA) is unknown. We predicted that VMA21 participates in OA via interacting with miR-103, an OA promoter. Therefore, we analyzed the crosstalk between VMA21 and miR-103 in OA. In this study, the levels of VMA21, pre-miR-103, and mature miR-103 in synovial fluid samples from OA patients (n = 56) and controls (n = 56) were analyzed using RT-qPCR. Nuclear and cytoplasm samples were prepared from chondrocytes, and VMA21 expression was detected by RT-PCR. RNA-RNA pulldown assay was applied to analyze the direct interaction between VMA21 and pre-miR-103. The involvement of VMA21 and miR-103 in lipopolysaccharide (LPS)-induced chondrocyte apoptosis and viability was analyzed using cell apoptosis assay and 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, respectively. We found that compared to the control group, VMA21 expression was decreased in OA, and miR-103 maturation was increased in OA. VMA21 could be detected in both nuclear and cytoplasm, and VMA21 directly interacted with pre-miR-103. VMA21 overexpression reduced miR-103 maturation. VMA21 suppressed the role of miR-103 in enhancing chondrocyte apoptosis and reducing cell viability after LPS treatment. In conclusion, VMA21 might suppress LPS-induced chondrocyte apoptosis in OA by decreasing the production of mature miR-103.