MicroRNA-320 regulates matrix metalloproteinase-13 expression in chondrogenesis and interleukin-1β-induced chondrocyte responses

作者：Meng, F.; Zhang, Z.; Chen, W.; Huang, G.; He, A.; Hou, C.; Long, Y.; Yang, Z.; Zhang, Z.; Liao, W.^*

来源：Osteoarthritis and Cartilage, 2016, 24(5): 932-941.

DOI：10.1016/j.joca.2015.12.012

• MiRNA-320
• Metalloproteinase-13
• Osteoarthritis
• Chondrogenesis
• Chondrocytes

Objective: Metalloproteinases (MMPs) are key regulators of osteoarthritis (OA) and collagen degradation and have been shown to participate in endochondral ossification. The aim of this study was to determine whether microRNA-320 (miR-320) regulates the expression of MMP-13 in chondrogenesis and inflammation. @@@ Experimental design: miR-320 expression was assessed in vitro, in the ATDC5 cell model of chondrogenesis and in interleukin-1 beta (IL-1 beta)-treated primary mouse chondrocytes (PMCs), and in vivo, in normal and OA human cartilage by in situ hybridization. ATDC5 and PMCs were transfected with miR-320 or its antisense inhibitor (anti-miR-320), respectively. The roles of activated MAP kinases (MAPK) and NF-kappa B were evaluated by using specific inhibitors. Direct interaction between miR-320 and its putative binding site in the 30-untranslated region (30-UTR) of Mmp-13 mRNA was confirmed by the luciferase reporter assay. @@@ Results: miR-320 expression was elevated in chondrogenic and hypertrophic ATDC5, while significantly reduced in OA cartilage compared with normal cartilage. Stimulation with IL-1 beta led to a significant reduction in miR-320 expression in PMCs. Upregulation of MMP-13 expression was correlated with downregulation of miR-320 expression in both PMCs and ATDC5. Overexpression of miR-320 suppressed the activity of a reporter construct containing the 30-UTR and inhibited MMP-13 expression in both ATDC5 and IL-1 beta -treated PMCs, while treatment with anti-miR-320 enhanced MMP-13 expression. NF-kappa B and MAPK activation downregulated miR-320 expression. @@@ Conclusion: Cartilage development and homeostasis are influenced by miR-320, which directly targets MMP-13 and regulates chondrogenesis and the IL-1 beta-stimulated catabolic effect in mouse chondrocytes.

• 出版日期2016-5
• 单位中山大学