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

Osteoarthritis and Cartilage
Fangang MengWeiming Liao

Abstract

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. miR-320 expression was assessed in vitro, in the ATDC5 cell model of chondrogenesis and in interleukin-1β (IL-1β)-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-κB were evaluated by using specific inhibitors. Direct interaction between miR-320 and its putative binding site in the 3'-untranslated region (3'-UTR) of Mmp-13 mRNA was confirmed by the luciferase reporter assay. miR-320 expression was elevated in chondrogenic and hypertrophic ATDC5, while significantly reduced in OA cartilage compared with normal cartilage. Stimulation with IL-1β 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. Overe...Continue Reading

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