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

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

  • J Hazard Mater. 2025 Dec 8:501:140750. doi: 10.1016/j.jhazmat.2025.140750.
Jialing Yu 1,  Sihan Huang 1,  Jianbin Zhang 1,  Zijian Su 1,  Yiming Chang 1,  Keke Liu 1,  Lu Yang 1,  Huiying Guo 2,  Jinshao Ye 1,  Xujing Liang 3,  Xiaojia Chen 4,  An Hong 5,  Yibo Zhang 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive molecules and Discovery of Innovative Drugs, Jinan University; National Engineering Research Center of Genetic Midicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, Guangdong provincial Biotechnology Drug & Engineering Technology Research Center, Jinan University Guangzhou 510632, China; Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
  • 2 Guangdong Key Laboratory of Environmental Pollution and Health, College of Environment and Climate, Jinan University, Guangzhou 510632, China; Center for Joint Surgery and Sports Medicine, the First Affiliated Hospital, Jinan University, College of Environment and Climate, Jinan University, Guangzhou 510632, China.
  • 3 Department of Anesthesia, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China.
  • 4 State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive molecules and Discovery of Innovative Drugs, Jinan University; National Engineering Research Center of Genetic Midicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, Guangdong provincial Biotechnology Drug & Engineering Technology Research Center, Jinan University Guangzhou 510632, China; Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China. Electronic address: [email protected].
  • 5 State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive molecules and Discovery of Innovative Drugs, Jinan University; National Engineering Research Center of Genetic Midicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, Guangdong provincial Biotechnology Drug & Engineering Technology Research Center, Jinan University Guangzhou 510632, China; Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China. Electronic address: [email protected].
  • 6 State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive molecules and Discovery of Innovative Drugs, Jinan University; National Engineering Research Center of Genetic Midicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, Guangdong provincial Biotechnology Drug & Engineering Technology Research Center, Jinan University Guangzhou 510632, China; Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China. Electronic address: [email protected].
PMID: 41380262 DOI: 10.1016/j.jhazmat.2025.140750
Abstract

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.

Keywords

Bile acid; Nonalcoholic fatty liver disease; Osteoarthritis; Oxidative stress; Perfluorooctane sulfonate.

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