Background: Intervertebral disc (IVD) degeneration is a common degenerative disease that can lead to collapse or herniation of the nucleus pulposus (NP) and result in radiculopathy in patients./nMethods: NP tissue and cells were isolated from patients and mice, and the expression profile of cortistatin (CST) was analysed. In addition, ageing of the NP was compared between 6-month-old WT and CST-knockout (CST^-/-) mice. Furthermore, NP tissues and cells were cultured to validate the role of CST in TNF-α-induced IVD degeneration. Moreover, in vitro and in vivo experiments were performed to identify the potential role of CST in mitochondrial dysfunction, mitochondrial ROS generation and activation of the NLRP3 inflammasome during IVD degeneration. In addition, NF-κB signalling pathway activity was tested in NP tissues and cells from CST^-/- mice./nResults: The expression of CST in NP cells was diminished in the ageing- and TNF-α-induced IVD degeneration process. In addition, compared with WT mice, aged CST^-/- mice displayed accelerated metabolic imbalance and enhanced apoptosis, and these mice showed a disorganized NP tissue structure. Moreover, TNF-α-mediated catabolism and apoptosis were alleviated by exogenous CST treatment. Furthermore, CST inhibited mitochondrial dysfunction in NP cells through IVD degeneration and suppressed activation of the NLRP3 inflammasome. In vitro and ex vivo experiments indicated that increased NF-κB pathway activity might have been associated with the IVD degeneration observed in CST^-/- mice./nConclusion: This study suggests the role of CST in mitochondrial ROS and activation of the NLRP3 inflammasome in IVD degeneration, which might shed light on therapeutic targets for IVD degeneration.

中文翻译：

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皮质抑素通过靶向线粒体ROS依赖的NLRP3炎性小体激活来防止椎间盘退变。

背景：椎间盘退变是一种常见的变性疾病，可导致髓核（NP）塌陷或突出，并导致患者发生神经根病。/n方法：从患者和小鼠中分离出NP组织和细胞，分析了皮质抑素（CST）的表达谱。此外，比较了6个月大的WT和CST基因敲除（CST ^-/-）小鼠的NP衰老。此外，培养了NP组织和细胞以验证CST在TNF-α诱导的IVD变性中的作用。而且，在体外和体内进行实验以鉴定CST在IVD变性期间在线粒体功能障碍，线粒体ROS生成和NLRP3炎性体活化中的潜在作用。此外，在CST ^-/-小鼠的NP组织和细胞中测试了NF-κB信号通路的活性。/n结果：在衰老和TNF-α诱导的IVD变性过程中，NP细胞中CST的表达减少了。此外，与野生型小鼠相比，CST年龄老^-/-小鼠表现出加速的代谢失衡和增强的细胞凋亡，并且这些小鼠表现出混乱的NP组织结构。此外，外源性CST治疗减轻了TNF-α介导的分解代谢和细胞凋亡。此外，CST通过IVD变性抑制NP细胞中的线粒体功能障碍，并抑制NLRP3炎性体的激活。体外和离体实验表明，NF-κB通路活性增加可能与CST ^-/-小鼠中观察到的IVD变性有关。/n结论：这项研究表明CST在线粒体ROS和NLRP3炎性小体活化中的作用在IVD变性中的作用，这可能为IVD变性的治疗目标提供了启示。