Osteoarthritis (OA) is a chronic disease that causes pain and functional impairment by affecting joint tissue. It is a significant global health issue, causing substantial economic and property losses. Despite extensive research, the underlying mechanisms of OA remain unclear. Recent studies have shown that pyroptosis, a form of programmed cell death, plays a crucial role in OA progression. Pyroptosis involves the activation of caspase-1, leading to the formation of inflammatory bodies, cell membrane perforation, and the release of inflammatory mediators such as IL-1β, IL-18, and MMP13. This process affects various cells and tissues, including synovial macrophages, fibroblast-like synoviocytes (FLS), chondrocytes, and subchondral osteoblasts, contributing to OA development. The molecular mechanisms of pyroptosis involve three pathways: canonical, non-canonical, and alternative. The canonical pathway is triggered by NLRP3 inflammasome activation, while the non-canonical pathway is initiated by caspase-11 or caspase-4/5. The alternative pathway is influenced by factors such as LPS and TRIF adapter. Pyroptosis is associated with the release of inflammatory factors, leading to synovial inflammation, cartilage degradation, and subchondral bone changes. The study highlights the role of pyroptosis in OA and suggests that targeting pyroptosis could offer new therapeutic approaches. The research also explores the interconnections between pyroptosis and various tissues, including synovium, cartilage, ECM, and subchondral bone. Understanding these mechanisms is essential for developing effective treatments for OA.Osteoarthritis (OA) is a chronic disease that causes pain and functional impairment by affecting joint tissue. It is a significant global health issue, causing substantial economic and property losses. Despite extensive research, the underlying mechanisms of OA remain unclear. Recent studies have shown that pyroptosis, a form of programmed cell death, plays a crucial role in OA progression. Pyroptosis involves the activation of caspase-1, leading to the formation of inflammatory bodies, cell membrane perforation, and the release of inflammatory mediators such as IL-1β, IL-18, and MMP13. This process affects various cells and tissues, including synovial macrophages, fibroblast-like synoviocytes (FLS), chondrocytes, and subchondral osteoblasts, contributing to OA development. The molecular mechanisms of pyroptosis involve three pathways: canonical, non-canonical, and alternative. The canonical pathway is triggered by NLRP3 inflammasome activation, while the non-canonical pathway is initiated by caspase-11 or caspase-4/5. The alternative pathway is influenced by factors such as LPS and TRIF adapter. Pyroptosis is associated with the release of inflammatory factors, leading to synovial inflammation, cartilage degradation, and subchondral bone changes. The study highlights the role of pyroptosis in OA and suggests that targeting pyroptosis could offer new therapeutic approaches. The research also explores the interconnections between pyroptosis and various tissues, including synovium, cartilage, ECM, and subchondral bone. Understanding these mechanisms is essential for developing effective treatments for OA.