Pyroptosis and Intervertebral Disc Degeneration: Mechanistic Insights and Therapeutic Implications

Abstract

Low back pain (LBP) is a common problem worldwide, resulting in great patient suffering and great challenges for the social health system. Intervertebral disc (IVD) degeneration (IVDD) is widely acknowledged as one of the key causes of LBP. Accumulating evidence suggests that aberrant pyroptosis of IVD cells is involved in the pathogenesis of IVDD progression, however, the comprehensive roles of pyroptosis in IVDD have not been fully established, leaving attempts to treat IVDD with anti-pyroptosis approaches questionable. In this review, we summarize the characteristics of pyroptosis and emphasize the effects of IVD cell pyroptosis on the pathological progression of IVDD, including secretion of cytokines, nucleus pulposus cell apoptosis and autophagy, accelerated extracellular matrix degradation, annulus fibrosus rupture, cartilage endplate calcification, vascularization, sensory and sympathetic fiber neoinnervation, and infiltrating lymphatic vessels. Finally, we discuss several interventions used to treat IVDD by targeting pyroptosis. This review provides novel insights into the crucial role of IVD cell pyroptosis in IVDD pathogenesis, and could be informative for developing novel therapeutic approaches for IVDD and LBP.

Relevance of pyroptosis‐associated genes in nasopharyngeal carcinoma diagnosis and subtype classification

“…Excessive pyroptosis, however, can trigger a severe inflammatory response that results in improper repair of damaged tissues and organs, resulting in a number of inflammatory diseases such as cancer, arthritis, atherosclerosis, sepsis and Parkinson's disease, amongst others. [18][19][20][21][22] In the present study, through a comprehensive review of pyroptosis-related genes (PRGs) in GSE53819 and GSE64634, acquired from the Gene Expression Omnibus (GEO) (https://www. ncbi.nlm.nih.gov/geo) database, we examined the function of PRGs in risk prediction and subtype classification of NPC patients.…”

“…Moderate levels of pyroptosis have been shown to help the body resist pathogen invasion and inflammatory responses mediated by inflammatory factors, which help maintain the stability of the internal environment. Excessive pyroptosis, however, can trigger a severe inflammatory response that results in improper repair of damaged tissues and organs, resulting in a number of inflammatory diseases such as cancer, arthritis, atherosclerosis, sepsis and Parkinson's disease, amongst others 18–22 …”

Catalytic Nanodots‐Driven Pyroptosis Suppression in Nucleus Pulposus for Antioxidant Intervention of Intervertebral Disc Degeneration

“…Previous studies have revealed that the over‐production ofreactive oxygen species (ROS), including hydrogen peroxide (H 2 O 2 ), superoxide anion (O 2 •− ), peroxynitrite (ONOO − ), and hydroxyl radical (•OH), significantly disrupts the homeostasis of IVD microenvironment and contributes profoundly to the pyroptosis of NP cells. [ 6–8 ] Particularly, pyroptosis not only provokes the degradation of ECM but also induces secondary inflammation in IVD, thereby complicating the IVD microenvironment and effective interventions. [ 9 ] Hence, we speculated that alleviating the pyroptosis of NP cells by reducing excessive ROS levels can be a promising target for alleviating IVDD.…”

hASCs-derived exosomal miR-155-5p targeting TGFβR2 promotes autophagy and reduces pyroptosis to alleviate intervertebral disc degeneration

“…Ge Y et al. assumed that autophagy regulated inflammasome activation and affected the outcome of cell pyroptosis [ 9 ]. Pyroptosis is a newly discovered form of programmed cell death, which is also involved in NP cells (NPCs) during IDD progression [ 10 ].…”