miR-5581 Contributes to Osteoarthritis by Targeting NRF1 to Disturb the Proliferation and Functions of Chondrocytes.

Chondrocyte survival is critical for the preservation of a healthy cartilage matrix. Limited chondrocyte function and survival can result in articular cartilage failure, thereby contributing to osteoarthritis (OA). In this study, miR-5581 was significantly up-regulated in OA samples, and miR-5581-associated genes were enriched in Kras signaling. miR-5581 up-regulation was observed in clinical OA samples and IL-1ß-stimulated chondrocytes. miR-5581 inhibition attenuated IL-1ß-induced chondrocyte proliferation suppression, extracellular matrix (ECM) synthesis suppression and degradation, and IL-1ß-suppressed Kras signaling activation. miR-5581 was targeted to inhibit NRF1. In IL-1ß-treated chondrocytes, NRF1 overexpression attenuated IL-1ß-induced cellular damage and partially abolished the effects of miR-5581 overexpression on IL-1ß-stimulated chondrocytes. NRF1 was down-regulated in knee joint cartilage of OA mice. In conclusion, miR-5581, which was up-regulated in OA samples and IL-1ß-stimulated chondrocytes, inhibited chondrocyte proliferation and ECM synthesis, and promoted ECM degradation through targeting NRF1, whereby Kras signaling might be involved.