Fibroblast growth factor 10 delays the progression of osteoarthritis by attenuating synovial fibrosis via inhibition of IL-6/JAK2/STAT3 signaling in vivo and in vitro

Synovial fibrosis is a driver in the progression of osteoarthritis (OA). Fibroblast growth factor 10 (FGF10) has prominent anti-fibrotic effects in many diseases. Thus, we explored the anti-fibrosis effects of FGF10 in OA synovial tissue. In vitro, fibroblast-like synoviocytes (FLSs) were isolated from OA synovial tissue and stimulated with TGF-& beta; to establish a cell model of fibrosis. After treatment with FGF10, we assessed the effects on FLS proliferation and migration using CCK-8, EdU, and scratch assays, and collagen production was observed using Sirius Red Stain. The JAK2/STAT3 pathway and expression of fibrotic markers were evaluated through western blotting (WB) and immunofluorescence (IF). In vivo, we treated mice with OA induced by surgical destabilization of the medial meniscus (DMM) with FGF10 and assessed the anti-OA effect using histological and immunohistochemical (IHC) staining of MMP13, and fibrosis was evaluated using HE and Masson's trichrome staining. The expression of IL-6/JAK2/STAT3 pathway components was determined using ELISA, WB, IHC, and IF. In vitro, FGF10 inhibited TGF-& beta;-induced FLS proliferation and migration, decreased collagen deposition, and improved synovial fibrosis. Moreover, FGF10 mitigated synovial fibrosis and improved the symptoms of OA in DMMinduced OA mice. Overall, FGF10 had promising anti-fibrotic effects on FLSs and improved OA symptoms in mice. The IL-6/STAT3/JAK2 pathway plays key roles in the anti-fibrosis effect of FGF10. This study is the first to demonstrate that FGF10 inhibited synovial fibrosis and attenuated the progression of OA by inhibiting the IL-6/ JAK2/STAT3 pathway.