2022, Vol. 26 ›› Issue (9): 1445-1451

Role and therapeutic implications of pyroptosis in intervertebral disc degeneration

Zhang Haobo1, 2, Zhao Yunan1, 2, Yang Xuejun2   

Abstract: BACKGROUND: Pyroptosis is a newly discovered type of pro-inflammatory programmed cell necrosis. It is found that cell pyroptosis plays an important role in the occurrence and development of intervertebral disc degeneration.
OBJECTIVE: To review the research progress on the molecular mechanism of pyroptosis, the role of pyroptosis in intervertebral disc degeneration, provide new ideas for the study of the mechanism of intervertebral disc degeneration, and provide new targets for the treatment of intervertebral disc degeneration.
METHODS: A computed-based online retrieval of PubMed, Wanfang, and CNKI databases were conducted with the keywords of “Pyroptosis, Intervertebral disc degeneration, Nucleus pulposus, Caspase-1, NLRP3, Gasdermin D, IL-1β” in English and Chinese, respectively. Finally, 66 articles were selected to review.
RESULTS AND CONCLUSION: (1) The typical activation pathway of cell pyroptosis plays an important role in the process of intervertebral disc degeneration. A variety of signal molecules stimulate intervertebral disc cells to activate NLRP3 and then activate caspase-1. Finally, it causes the production of IL-1β, which eventually leads to pyroptosis and increased extracellular matrix catabolism, so as to promote intervertebral disc degeneration. (2) Signal molecules in the process of pyrolysis include chemical stimulation (such as lipopolysaccharide, reactive oxygen species, advanced glycation end products, interleukin-1β and tumor necrosis factor-α) and mechanical stimulation (such as mechanical stretching). (3) A variety of signaling pathways are activated in the process of cell pyroptosis, such as nuclear factor-κB pathway and Wnt/ β-catenin pathway.   (4) The occurrence of pyroptosis can be inhibited by different action targets, such as nuclear factor-κB inhibitor Bay11-7082, SN50, NLRP3 inhibitor MCC950, exosomes derived from mesenchymal stem cells miRNA-410, and melatonin. (5) The detailed mechanism of cell pyroptosis leading to intervertebral disc degeneration is still unclear, and the role of atypical cell pyroptosis pathway in intervertebral disc degeneration still needs to be further explored. (6) The therapeutic effect of cytolytic targeted drugs on intervertebral disc degeneration has been verified in cell and animal models, but it has not been applied in clinic. (7) With the further research, targeted drugs for pyroptosis may become a promising treatment strategy for degenerative disc disease.

Key words:pyroptosis, intervertebral disc degeneration, nucleus pulposus, extracellular matrix, activation, signal, interleukin-1β