Perfluorooctane sulfonate induces joint inflammation to trigger osteoarthritis through the YAP1/IκBα signaling pathway.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are persistent pollutants that have been linked to chronic inflammation. Epidemiologic studies have indicated that PFAS exposure is associated with an increased prevalence of osteoarthritis (OA). We previously hypothesized that inflammation may facilitate the penetration of perfluorooctane sulfonate (PFOS) across the joint barrier; however, the potential impact of PFASs on OA progression remains unclear. Herein, we revealed that exposure to PFOS induced joint inflammation, contributing to the development of OA in vivo; PFOS decreased the expression of YAP1 and IκBα, causing inflammation of the synovium and cartilage. The regulation of OA by PFOS is conserved in human synovicytes, synovial explants, and mice. Our findings clarify the hazards and potential mechanisms of PFOS towards joint inflammation and highlight YAP1/IκBα as a potential therapeutic target for OA.