Bilirubin ameliorates osteoarthritis via activating Nrf2/HO‐1 pathway and suppressing NF‐κB signalling

• Published in: Journal of cellular and molecular medicine 2024-04, Vol.28 (7), p.e18173-n/a
• Main Authors: Zhao, Xinyu, Duan, Baiqun, Wu, Jianing, Huang, Lihui, Dai, Sheng, Ding, Jie, Sun, Meng, Lin, Xinlu, Jiang, Yiling, Sun, Tuyue, Lu, Ruijie, Huang, Huirong, Lin, Guangyong, Chen, Ruijie, Yao, Qing, Kou, Longfa
• Format: Article
• Language: English
• Subjects: Antibodies; antioxidant; Antioxidants; anti‐inflammation; Apoptosis; Arthritis; Bilirubin; Bilirubin - pharmacology; Biotechnology; Cartilage; Cartilage diseases; Cell viability; Chondrocytes; Chondrocytes - metabolism; Enzymes; Free radicals; Humans; Hydrogen peroxide; Inflammation; Inflammation - drug therapy; Interleukin-1beta - pharmacology; Joint diseases; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Metabolism; Microenvironments; NF-E2-Related Factor 2 - metabolism; NF-kappa B - metabolism; NF-κB protein; Nrf2/HO‐1; Original; Osteoarthritis; Osteoarthritis - drug therapy; Osteoarthritis - metabolism; Oxidative stress; Penicillin; Proteins; Reactive oxygen species; Reactive Oxygen Species - metabolism; Signal transduction; Stains & staining
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/jcmm.18173

Osteoarthritis (OA) is a chronic degenerative joint disease that affects worldwide. Oxidative stress plays a critical role in the chronic inflammation and OA progression. Scavenging overproduced reactive oxygen species (ROS) could be rational strategy for OA treatment. Bilirubin (BR) is a potent endogenous antioxidant that can scavenge various ROS and also exhibit anti‐inflammatory effects. However, whether BR could exert protection on chondrocytes for OA treatment has not yet been elucidated. Here, chondrocytes were exposed to hydrogen peroxide with or without BR treatment. The cell viability was assessed, and the intracellular ROS, inflammation cytokines were monitored to indicate the state of chondrocytes. In addition, BR was also tested on LPS‐treated Raw264.7 cells to test the anti‐inflammation property. An in vitro bimimic OA microenvironment was constructed by LPS‐treated Raw264.7 and chondrocytes, and BR also exert certain protection for chondrocytes by activating Nrf2/HO‐1 pathway and suppressing NF‐κB signalling. An ACLT‐induced OA model was constructed to test the in vivo therapeutic efficacy of BR. Compared to the clinical used HA, BR significantly reduced cartilage degeneration and delayed OA progression. Overall, our data shows that BR has a protective effect on chondrocytes and can delay OA progression caused by oxidative stress.