The regulatory role and therapeutic application of pyroptosis in musculoskeletal diseases

Pyroptosis is a controlled form of inflammatory cell death characterized by inflammasome activation, pore formation, and cell lysis. According to different caspases, pyroptosis can be divided into canonical, non-canonical, and other pathways. The role of pyroptosis in disease development has been paid more attention in recent years. The trigger factors of pyroptosis are often related to oxidative stress and proinflammatory substances, which coincide with the pathological mechanism of some diseases. Pyroptosis directly leads to cell lysis and death, and the release of cytosolic components and proinflammatory cytokines affects cell activity and amplifies the inflammatory response. All the above are involved in a series of basic pathological processes, such as matrix degradation, fibrosis, and angiogenesis. Since these pathological changes are also common in musculoskeletal diseases (MSDs), emerging studies have focused on the correlations between pyroptosis and MSDs in recent years. In this review, we first summarized the molecular mechanism of pyroptosis and extensively discussed the differences and crosstalk between pyroptosis, apoptosis, and necrosis. Next, we elaborated on the role of pyroptosis in some MSDs, including osteoarthritis, rheumatoid arthritis, osteoporosis, gout arthritis, ankylosing spondylitis, intervertebral disc degeneration, and several muscle disorders. The regulation of pyroptosis could offer potential therapeutic targets in MSDs treatment. Herein, the existing drugs and therapeutic strategies that directly or indirectly target pyroptosis pathway components have been discussed in order to shed light on the novel treatment for MSDs.