Downregulation of miR-3680-3p inhibits the progression of osteoarthritis via targeting OGG1

Abstract

Background: Osteoarthritis (OA) is a degenerative joint disease that seriously endangers the health of middle-aged and elderly people. MicroRNA (miRNA) regulation is associated with several diseases, including OA. This study aimed to explore the role and mechanism of miR-3680-3p in regulating OA progression.

Methods: GSE105027 and GSE143514 were downloaded from Gene Expression Omnibus (GEO) and differentially expressed miRNAs between control and OA-affected cartilage were obtained by R software. GSE55235 gene expression profile was downloaded and analyzed the differentially expressed genes. In vitro study, chondrocyte was administrated by interleukin-1β (IL-1β) to mimic an in vitro model of OA. The apoptotic and cell cycle arrest were assessed by flowcytometry. IL-6 and TNF-α expressions were measured by the enzyme-linked immunosorbant assay (ELISA). Moreover, the OA rat model was established to explore the function of miR-3680-3p/OGG1 axis in vivo.

Results: GSE105027 identified 266 differentially expressed miRNAs and GSE143514 identified 160 differentially expressed miRNAs. MiR-3680-3p was significantly upregulated in OA samples in comparison to normal cartilage samples. IL-1β significantly reduced the cell viability than control chondrocytes, this effect was reversed by miR-3680-3p antagomir. Treatment with miR-3680-3p antagomir could partially reversed the IL-1β-induced promotion of apoptosis of chondrocytes. IL-1β increased the expression of MMP1 and MMP13, while the expression of matrix related protein, such as aggrecan, was significantly downregulated in IL-1β-treated chondrocytic cells. Inhibition of miR-3680-3p expression by an antagomir could reverse this phenotype. OGG1 was predicted and verified as a direct target of miR-3680-3p. Moreover, our in vivo study found that after knockdown of miR-3680-3p alleviated the development of OA in rat models.

Conclusion: Inhibition of miR-3680-3p reversed the IL-1β induced chondrocytes injury and delayed the progression of OA via targeting OGG1.

Keywords: Chondrocytes; OGG1; miR-3680–3p.