Abstract
Recent studies have revealed novel forms of cell death beyond the canonical types of cellular apoptosis and necrosis, and these novel forms of cell death are induced by extreme microenvironmental factors. Pyroptosis, a type of regulated cell death, occurs when pattern recognition receptors (PRRs) induce the activation of cysteine-aspartic protease 1 (caspase-1) or caspase-11, which can trigger the release of the pyrogenic cytokines interleukin-1β (IL-1β) and IL-18. Osteoarthritis (OA), the most common joint disease worldwide, is characterized by low-grade inflammation and increased levels of cytokines, including IL-1β and IL-18. Additionally, some damaged chondrocytes associated with OA exhibit morphological changes consistent with pyroptosis, suggesting that this form of regulated cell death may contribute significantly to the pathology of OA. This review summarizes the molecular mechanisms of pyroptosis and shows the critical role of NLRP3 (NLR family, pyrin domain containing 3; NLR refers to “nucleotide-binding domain, leucine-rich repeat”) inflammasomes. We also provide evidence describing potential role of pyroptosis in OA, including the relationship with OA risk factors and the contribution to cartilage degradation, synovitis and OA pain.
Highlights
Cell death is one of the most fundamental physiological processes used by multicellular organisms to maintain homeostasis, as exemplified by tissue sculpting during embryologic development and the elimination of senescent cells
Much higher levels of NLRP3 are found in the synovium in OA joints than in normal joints, suggesting that macrophage pyroptosis is closely related to synovial inflammation
Pyroptotic cells release IL-1β and IL-18 into the synovial fluid following the activation of caspase-1
Summary
Cell death is one of the most fundamental physiological processes used by multicellular organisms to maintain homeostasis, as exemplified by tissue sculpting during embryologic development and the elimination of senescent cells. Recent studies have revealed several other types of cell death, including autophagy [8], necroptosis [9], pyroptosis [10], ferroptosis [11], mitochondrial permeability transition (MPT)-dependent necrosis [12] and parthanatos [13]. The pathological changes associated with OA affect all tissues in the joint and include cartilage degeneration, subchondral sclerosis, variable degrees of synovial inflammation, osteophyte formation and hypertrophy of the whole joint capsule [18] Inflammasomes such as NLRP3 (NLR family, pyrin domain containing 3; NLR refers to “nucleotide-binding domain, leucine-rich repeat”), which are induced by nuclear factor kappa B (NF-κB) signaling and can convert interleukin-1β (IL-1β) and IL-18 into mature proinflammatory cytokines, are considered a factor in low-grade inflammatory pathology [19]. Because no efficient treatment option is currently available for OA, an understanding of pyroptosis and related signaling factors might be useful in clinical decision-making
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
