Orthopedic Center, The First Affiliated Hospital of Soochow University, Suzhou 215000, China.
Kunshan Hospital of Traditional Chinese Medicine, Kunshan 215300, China.
Oxid Med Cell Longev. 2021 Feb 1;2021:4657014. doi: 10.1155/2021/4657014. eCollection 2021.
Our previous study verified the occurrence of (. ), a low-virulence anaerobic bacterium, latently residing in degenerated intervertebral discs (IVDs), and the infection had a strong association with IVD degeneration. We explored whether . induces nucleus pulposus cell (NPC) pyroptosis, a more dangerous cell death process than apoptosis, and accelerates IVD degeneration via the pyroptotic products interleukin- (IL-) 1 and IL-18. After coculturing with . , human NPCs showed significant upregulation of NOD-like receptor 3 (NLRP3), cleaved IL-1, cleaved caspase-1, and cleaved gasdermin D in response to the overexpression of IL-1 and IL-18 in a time- and dose-dependent manner. In addition, the gene expression of inflammatory factors and catabolic enzymes significantly increased in normal NPCs when cocultured with pyroptotic NPCs in a transwell system, and the adverse effects were inhibited when NPC pyroptosis was suppressed. Furthermore, inoculation of . into the IVDs of rats caused significant pyroptosis of NPCs and remarkable IVD degeneration. Finally, coculture of NPCs with . induced the overexpression of reactive oxygen species (ROS) and NLRP3, while inhibition of both factors reduced NPC pyroptosis. Therefore, . induces NPC pyroptosis via the ROS-NLRP3 signaling pathway, and the pyroptotic NPCs cause an IVD degeneration cascade. Targeting the . -induced pyroptosis of NPCs may become an alternative treatment strategy for IVD degeneration in the future.
我们之前的研究证实了一种低毒厌氧细菌（. ）的存在，这种细菌潜伏在退变的椎间盘（IVD）中，与 IVD 退变有很强的关联。我们探讨了. 是否会诱导髓核细胞（NPC）发生细胞焦亡，这是一种比细胞凋亡更危险的细胞死亡过程，并通过细胞焦亡产物白细胞介素-1（IL-1）和 IL-18 加速 IVD 退变。在与. 共培养后，人 NPC 以时间和剂量依赖的方式显著上调 NOD 样受体 3（NLRP3）、切割的 IL-1、切割的半胱天冬酶-1 和切割的 GSDMD，从而对 IL-1 和 IL-18 的过度表达做出反应。此外，在 Transwell 系统中，正常 NPC 与发生细胞焦亡的 NPC 共培养时，炎症因子和分解代谢酶的基因表达显著增加，而当抑制 NPC 细胞焦亡时，不良影响被抑制。此外，将. 接种到大鼠的 IVD 中会导致 NPC 发生明显的细胞焦亡和显著的 IVD 退变。最后，NPC 与. 共培养会诱导活性氧（ROS）和 NLRP3 的过表达，而抑制这两个因素会减少 NPC 细胞焦亡。因此，. 通过 ROS-NLRP3 信号通路诱导 NPC 细胞焦亡，而发生细胞焦亡的 NPC 会引发 IVD 退变级联反应。针对. 诱导的 NPC 细胞焦亡可能成为未来治疗 IVD 退变的一种替代策略。
