Downregulation of microRNA-9 increases Matrix metalloproteinase-13 expression levels and facilitates osteoarthritis onset

Abstract

Matrix metalloproteinase-13 (MMP-13) degrades collagen and other matrix components, thus playing a critical role in the development of osteoarthritis (OA). The expression level of microRNA-9 (miR-9) is significantly depressed in cartilage tissues of OA patients. Furthermore, bioinformatics analysis demonstrated complementary binding sites between miR-9 and MMP-13. The current study, therefore, investigated whether miR-9 is involved in regulating MMP-13 expression levels and OA onset. Cartilage tissues from OA patients and healthy individuals were compared for miR-9, MMP-13 and collagen type II α1 chain (Col2A1) expression levels. A dual luciferase gene reporter assay was performed to evaluate the association between miR-9 and MMP-13. Sodium iodoacetate was injected into the knee joint cartilage tissues to generate the rat OA model. The expression levels of miR-9, MMP-13 and Col2A1 were compared between the model and control rats. In addition, the OA model rats received miR-9 agomir for further expressional assay. Cartilage tissue samples from the OA patients exhibited significantly lower miR-9 and Col2A1 expression levels when compared with the control rats, whilst the expression level of MMP-13 was upregulated. As the target gene of miR-9, MMP-13 is under the targeted regulation of miR-9. The injection of miR-9 agomir into the knee joint cavity significantly depressed MMP-13 expression in the cartilage tissues of OA rats, with reduced collagen degradation and enhanced COL2A1. OA cartilage tissues have lower miR-9 expression and higher MMP-13 expression levels. Thus, miR-9 inhibits the expression level of MMP-13, decreases its inhibitory effects on COL2A1, and therefore contributes to antagonizing OA.