Inhibition of PI3K/Akt/mTOR signaling by curcumin: a novel approach to mitigate synovial fibrosis in knee osteoarthritis

Curcumin (CUR) is used in treating knee osteoarthritis (KOA), but its effects on synovial fibrosis and underlying mechanisms remain unclear. In vivo, a rat KOA model was established via anterior cruciate ligament transection (ACLT), followed by CUR administration. Synovial fibrosis, autophagy, and PI3K/AKT/mTOR pathway were assessed. In vitro, TGF-β1-induced fibroblast-like synoviocytes (FLSs) were treated with CUR. Fibrosis markers, autophagy activity, and PI3K/AKT/mTOR pathway proteins were analyzed. CUR alleviated synovial fibrosis in ACLT-induced rats. In FLSs, CUR reduced TGF-β1-stimulated fibrosis, suppressed PI3K/Akt/mTOR signaling, and enhanced autophagy. In vivo results confirmed CUR inhibited PI3K/Akt/mTOR and activated autophagy. CUR attenuated synovial fibrosis by activating protective autophagy via inhibition of the PI3K/Akt/mTOR pathway, elucidating a novel anti-fibrotic mechanism for KOA therapy.