Search

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-1β-stimulated chondrocytes. miR-5581 inhibition attenuated IL-1β-induced chondrocyte proliferation suppression, extracellular matrix (ECM) synthesis suppression and degradation, and IL-1β-suppressed Kras signaling activation. miR-5581 was targeted to inhibit NRF1. In IL-1β-treated chondrocytes, NRF1 overexpression attenuated IL-1β-induced cellular damage and partially abolished the effects of miR-5581 overexpression on IL-1β-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-1β-stimulated chondrocytes, inhibited chondrocyte proliferation and ECM synthesis, and promoted ECM degradation through targeting NRF1, whereby Kras signaling might be involved., (Copyright © 2023 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Our study aimed at validating the effect of WISP1 on osteoarthritis (OA) and the pathway involved in the WISP1-induced protection against OA. The expression of WISP1 was measured by immunohistochemical analyses. We found that WISP1 expression was shown to be upregulated within human OA cartilage compared with controls. WISP1 expression was related to knee OA severity. rhWISP1 inhibited OA chondrocyte senescence and apoptosis in vitro, which was reversed by the αvβ3 antibody and PI3K/Akt inhibitor LY294002. WISP1 overexpression induced by knee injection of LiCI could also prevent the senescence and apoptosis of rat chondrocytes. Safranin-O staining and Mankin score revealed that WISP1 overexpression can protect rat chondrocytes from degeneration. Nearly opposite results were obtained in the treatment of ICG-001 and siRNA-WISP1 in vivo. These data strongly suggest that WISP1 can protect against the senescence and apoptosis of chondrocytes via modulating the αvβ3 receptor and PI3K/Akt signaling pathway within OA. Therefore, the development of specific activators of WISP1 may present the value of an underlying OA treatment. [ABSTRACT FROM AUTHOR]