Bile acids insufficiency links perfluorooctane sulfonate-induced oxidative stress-mediated fatty liver with osteoarthritis.

Perfluoroalkyl substances (PFAS) are ubiquitously distributed and persistent environmental pollutants. Articular injury caused by numerous environmental pollutants has been reported; however, whether and how PFAS damage joints have yet to be determined. Here, we revealed that exposure to perfluorooctane sulfonate (PFOS) caused osteoarthritis (OA) within the zebrafish anal fin. Mechanistically, PFOS induces oxidative stress in the liver, which decreases bile acid synthesis and transport and causes lipid accumulation. Additionally, exposure to PFOS disturbs the gut microbiota, which may further reduce the production of secondary bile acids. This bile acid insufficiency may limit the activation of farnesoid X receptor (FXR) and the downstream glucagon-like peptide 1 receptor (GLP-1R) in chondrocytes and thereby facilitate the development of OA. Furthermore, we found that by scavenging reactive oxygen species (ROS), astaxanthin (AX) significantly reversed PFOS-induced OA and hepatic steatosis. Our findings elucidated the harmful effects and underlying mechanisms of PFOS on articular health and highlighted ROS scavenging as a therapeutic strategy for PFOS-induced OA.