The article explores the role of pyroptosis in the progression of osteoarthritis (OA), a chronic disease affecting joint tissue and causing significant economic and functional losses. Pyroptosis, a form of inflammatory cell death, is influenced by three pathways: canonical, non-canonical, and alternative. The canonical pathway involves the assembly of inflammatory complexes through the activation of NLRP3 inflammasome, while the non-canonical pathway is initiated by caspase-11 or caspase-4/5. The alternative pathway is regulated by cFLIP, a protein that controls caspase-8 activation. Pyroptosis is triggered by various stimuli, including lipopolysaccharides (LPS) and ATP, and leads to the release of inflammatory factors such as IL-1β and IL-18. The study highlights the involvement of pyroptosis in synovial inflammation, chondrocyte death, and subchondral bone changes in OA. Macrophages, fibroblast-like synoviocytes (FLS), and chondrocytes are key cells affected by pyroptosis, with macrophages potentially preferentially undergoing pyroptosis. The article discusses the molecular mechanisms of pyroptosis and its therapeutic implications, emphasizing the need for targeted interventions to reduce inflammation and alleviate pain in OA patients.The article explores the role of pyroptosis in the progression of osteoarthritis (OA), a chronic disease affecting joint tissue and causing significant economic and functional losses. Pyroptosis, a form of inflammatory cell death, is influenced by three pathways: canonical, non-canonical, and alternative. The canonical pathway involves the assembly of inflammatory complexes through the activation of NLRP3 inflammasome, while the non-canonical pathway is initiated by caspase-11 or caspase-4/5. The alternative pathway is regulated by cFLIP, a protein that controls caspase-8 activation. Pyroptosis is triggered by various stimuli, including lipopolysaccharides (LPS) and ATP, and leads to the release of inflammatory factors such as IL-1β and IL-18. The study highlights the involvement of pyroptosis in synovial inflammation, chondrocyte death, and subchondral bone changes in OA. Macrophages, fibroblast-like synoviocytes (FLS), and chondrocytes are key cells affected by pyroptosis, with macrophages potentially preferentially undergoing pyroptosis. The article discusses the molecular mechanisms of pyroptosis and its therapeutic implications, emphasizing the need for targeted interventions to reduce inflammation and alleviate pain in OA patients.