MiR-203 regulates estrogen receptor α and cartilage degradation in IL-1β-stimulated chondrocytes

Introduction Estrogen receptor alpha (ER alpha) plays important roles in the etiology of osteoarthritis (OA), in which cartilage degradation and cellular inflammation are involved. MiR-203 is reported to direct target ER alpha, but its roles in chondrocytes remain uncovered. Methods In this study, ELISA showed that the level of estrogen hormone in the serum of postmenopausal OA patients was significantly lower than the one in patients without OA. RT-PCR revealed that the expression level of miR-203 was significantly up-regulated in the OA patients. Furthermore, western blotting demonstrated the lower expression levels of aggrecan, Col2A1, and ER alpha in the isolated articular cartilage tissues of OA patients. To decipher the association between ER alpha and miR-203 in the pathogenesis of OA, IL-1 beta stimulated cultured chondrocyte cell model was established to measure the cell viability, cellular inflammation, cell injury, as well as cartilage degradation with miR-203 inhibitor and ER alpha. Results The results showed that IL-1 beta stimulation induced the expression of miR-203, which promoted cellular inflammation and cell injury, and caused down-regulation of aggrecan and Col2A1. Luciferase assay indicated the direct binding between miR-203 and ER alpha, and ER alpha-specific SiRNA inversed the protective role of miR-203 inhibitor in the progression of OA in the cell system. Conclusions MiR-203 is critical in the onset and progression of OA, at least in part, caused by estrogen deficiency and ER alpha instability in OA patients, providing a novel therapeutic target for the treatment of OA.