MicroRNA-449a upregulation promotes chondrocyte extracellular matrix degradation in osteoarthritis

Osteoarthritis (OA) is a highly prevalent chronic and degenerative joint disease characterized by the continuous destruction of the articular cartilage. MicroRNAs (miRNAs) have been reported to be strongly involved in the pathogenesis of OA. The aim of this study was to explore whether miR-449a regulates the expression of growth differentiation factor5 (GDF5), which promotes chondrocyte extracellular matrix (ECM) degradation. We found that miR-449a expression was upregulated in OA cartilage compared to that in normal cartilage. Overexpression of miR-449a increased the expression of chondrocyte ECM catabolic factors, such as matrix metalloproteinases and a disintegrin and metalloproteinase with thrombospondin motif, while inhibiting that of anabolic genes, such as type II collagen and aggrecan. In contrast, suppression of miR-449a exerted the opposite effects. Moreover, GDF5 was identified as a direct target of miR-449a, and its expression was significantly suppressed by miR-449a overexpression. In addition, the suppression of chondrocyte ECM degradation induced by miR-449a inhibitor was attenuated by small interfering RNA-mediated knockdown of GDF5. Overall, these results suggest that miR-449a contributes to chondrocyte ECM degradation in OA via directly targeting GDF5, thereby providing insights to a promising therapeutic target for the treatment of human OA.