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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\u2010inflammatory 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\u2010treated Raw264.7 cells to test the anti\u2010inflammation property. An in\u00a0vitro bimimic OA microenvironment was constructed by LPS\u2010treated Raw264.7 and chondrocytes, and BR also exert certain protection for chondrocytes by activating Nrf2\/HO\u20101 pathway and suppressing NF\u2010\u03baB signalling. An ACLT\u2010induced OA model was constructed to test the in\u00a0vivo 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.<\/jats:p>","DOI":"10.1111\/jcmm.18173","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T02:50:01Z","timestamp":1710730201000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Bilirubin ameliorates osteoarthritis via activating Nrf2\/HO\u20101 pathway and suppressing NF\u2010\u03baB signalling"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0978-7677","authenticated-orcid":false,"given":"Xinyu","family":"Zhao","sequence":"first","affiliation":[{"name":"Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Key Laboratory of Structural Malformations in Children of Zhejiang 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