Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Biochem Biophys Res Commun. 2021 Jun 25;559:106-112. doi: 10.1016/j.bbrc.2021.04.090. Epub 2021 Apr 30.
Intervertebral disc degeneration (IDD) is a major cause of lower back pain (LBP), a condition that causes a heavy economic burden globally. The production of cytokines, including interleukin (IL)-1β and tumor necrosis factor (TNF) α, is increased in the degenerating intervertebral disc. Thioredoxin-interacting protein (TXNIP) participates in NLRP3 inflammasome-dependent pyroptosis in liver. Therefore, we hypothesized that TXNIP maypromote pyroptosis via NLRP3/Caspase-1/IL-1β signaling pathway in nucleus pulposus (NP) cell. This study examined the effects of TXNIP on IDD, explored the underlying mechanisms of action and find Morin which is the inhibitor of TXNIP can attenuates pyroptosis of nucleus pulposus cells and ameliorates intervertebral disc degeneration. Our findings indicate that TXNIP promote pyroptosis via NLRP3/Caspase-1/IL-1β signaling pathway in NP cell. Morin considerably inhibited the TXNIP/NLRP3/Caspase-1 signaling pathway in vitro. In vivo. Our data show that TXNIP can aggravates intervertebral disc degeneration and morin may be a useful therapeutic agent for IDD.
椎间盘退变（IDD）是导致下腰痛（LBP）的主要原因，这种疾病在全球造成了沉重的经济负担。退变的椎间盘会增加细胞因子的产生，包括白细胞介素（IL）-1β和肿瘤坏死因子（TNF）α。硫氧还蛋白相互作用蛋白（TXNIP）参与了肝脏中 NLRP3 炎性小体依赖性细胞焦亡。因此，我们假设 TXNIP 可能通过 NLRP3/Caspase-1/IL-1β 信号通路促进髓核细胞的细胞焦亡。本研究探讨了 TXNIP 对 IDD 的影响，探索了其作用机制，并发现 TXNIP 的抑制剂 Morin 可以减轻髓核细胞的细胞焦亡，改善椎间盘退变。我们的研究结果表明，TXNIP 通过 NLRP3/Caspase-1/IL-1β 信号通路促进 NP 细胞的细胞焦亡。Morin 在体外显著抑制了 TXNIP/NLRP3/Caspase-1 信号通路。在体内，我们的数据表明 TXNIP 可以加重椎间盘退变，Morin 可能是 IDD 的一种有用的治疗药物。
