Intervertebral disc degeneration (IDD) is characterized by the decrease of nucleus pulposus cells (NPCs).With the increase of the degree of degeneration, the reactive oxygen species (ROS) in nucleus pulposus tissue increases. Pyroptosis is a newly discovered form of cell death and its relationship with oxidative stress in NPCs remains unclear. This study was performed to investigate the mechanisms of pyroptosis of NPCs under oxidative stress. NPCs were isolated from IDD patients by surgical treatment. Pyroptosis related proteins like NLR family pyrin domain containing 3(NLRP3) and PYD and CARD domain containing (PYCARD) were detected by western blot, and membrane pore formation was observed by hochest33342/PI double staining or scanning electron microscope. The results showed that ROS induced the pyroptosis of NPCs and it depended on the expression of NLRP3 and PYCARD. The increased ROS level also increased transcription factor nuclear factor, erythroid 2 like 2 (NFE2L2, Nrf2) and the autophagy of NPCs, both of which attenuated the pyroptosis. In summary, ROS induces the pyroptosis of NPCs through the NLRP3/ PYCARD pathway, and establishes negative regulation by increasing autophagy and NFE2L2. These findings may provide a better understanding of the mechanism of IDD and potential therapeutic approaches for IDD treatment.

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Intervertebral disc degeneration (IDD) is closely associated with aging. Our previous studies have confirmed that heme oxygenase‐1 (HO‐1) can inhibit nucleus pulposus (NP) cell apoptosis. However, whether or not HO‐1 is involved in NP cell senescence and autophagy is unclear. Our results indicated that HO‐1 expression was reduced in IDD tissues and replicative senescent NP cells. HO‐1 overexpression using a lentiviral vector reduced the NP cell senescence level, protected mitochondrial function, and promoted NP cell autophagy through the mitochondrial pathway. Autophagy inhibitor 3‐MA pretreatment reversed the anti‐senescent and protective effects on the mitochondrial function of HO‐1, which promoted the degradation of the extracellular matrix (ECM) in the intervertebral disc. In vivo, HO‐1 overexpression inhibited IDD and enhanced autophagy. In summary, these results suggested that HO‐1 overexpression alleviates NP cell senescence by inducing autophagy via the mitochondrial route.