Resolvin D1 inhibits the proliferation of osteoarthritis fibroblast-like synoviocytes through the Hippo-YAP signaling pathway

Abstract

ObjectiveOsteoarthritis (OA) is a disease characterized by cartilage degradation and structural destruction. Resolvin D1 (RvD1), a specialized proresolving mediator (SPM) derived from omega-3 fatty acids, has been preliminarily proven to show anti-inflammatory and antiapoptotic effects in OA. However, the mechanisms of RvD1 in osteoarthritis fibroblast-like synoviocytes (OA-FLSs) need to be clarified.MethodsSynovial and fibroblast-like synoviocytes were obtained from OA patients and healthy individuals. MTT and EdU assays were performed to determine cell cytotoxicity and proliferation. The protein expression levels of cyclin D1, cyclin B1, PCNA, p53, MMP-13, YAP, p-YAP, and LATS1 were detected by western blot analysis. The release levels of IL-1β were detected by ELISA. The cell cycle was assessed by flow cytometry. Immunofluorescence was used to detect the levels of YAP in OA-FLSs.ResultsRvD1 inhibited OA-FLS proliferation and reduced MMP-13 and IL-1β secretion in the concentrations of 20 nM and 200 nM. Furthermore, RvD1 induced G2 cell cycle arrest in OA-FLSs via the Hippo-YAP signaling pathway and promoted YAP phosphorylation. However, RvD1 had no effects on normal FLSs.ConclusionsRvD1 inhibits OA-FLS proliferation by promoting YAP phosphorylation and protects chondrocytes by inhibiting the secretion of MMP-13 and IL-1β, providing an experimental basis for RvD1 treatment of OA.