Inhibition of miR-203 ameliorates osteoarthritis cartilage degradation in the postmenopausal rat model: involvement of estrogen receptor α.

MiR-203 is known to target estrogen receptor α (ERα) in various cancer cell lines, such as MCF-7. However, whether miR-203 regulates ERα and contributes to the onset and progression of osteoarthritis (OA) is poorly understood. A combined protocol of the bilateral ovariectomy and the intra-articular monosodium iodoacetate (MIA) injection was applied to establish a postmenopausal OA model in rats. Real-time quantitative PCR was used to detect miR-203 and mRNAs and Western blotting was exploited to quantify the expressions on the protein level. ELISA assays were deployed to detect the expression of MMP-1, MMP-3, PGE2 and CTX-II in serum samples. Dual-luciferase reporter assay was utilized to confirm the direct binding of miR-203 on ERα in postmenopausal OA rats. Expression of miR-203 was elevated; while ERα mRNA and protein were down-regulated in postmenopausal OA rats, compared to sham rats. Dual-luciferase reporter assay confirmed miR-203 bound and negatively regulated ERα, resulting in promoted cellular inflammation and cartilage destruction in postmenopausal OA rats. Suppression of miR-203 using a specific inhibitor ameliorated cartilage degradation in postmenopausal OA rats. MiR-203 is pivotal in the onset and progression of OA in the postmenopausal rat model, and holds promise for a therapeutic target of OA treatment.