Inhibiting the expression of GPR43 in macrophages can alleviate osteoarthritis by suppressing the M1 polarization and suppressing ROS production.

G-protein-coupled receptor 43 (GPR43) plays an important role in immunomodulation, metabolic regulation and ROS production. Our research aims to explore the role and mechanism of GPR43 in osteoarthritis (OA). We experimentally determined that following the intervention of macrophages with lipopolysaccharide (LPS), there is a significant upregulation in the expression of GPR43. GPR43 knockdown in macrophages can inhibit the M1 polarization and reactive oxygen species (ROS) production. Meanwhile, GPR43 knockdown can alleviate osteoarthritis in destabilized medial meniscus (DMM) induced OA mouse models. In mechanism, GPR43 knockdown in macrophages can inhibit the expression of CX3C chemokine ligand 1 (CX3CL1) and the activation of NF-κB signaling pathway, thereby exerting a therapeutic effect on OA. Overall, knockdown of GPR43 in macrophages can alleviate OA by inhibiting M1 polarization and ROS production via the CX3CL1/NF-κB signaling pathway. GPR43 is a potential therapeutic target for OA.