S100A9 induces nucleus pulposus cell degeneration through activation of the NF-κB signaling pathway.
S100A9 induces nucleus pulposus cell degeneration through activation of the NF-κB signaling pathway.
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S100A9 通过激活 NF-κB 信号通路诱导髓核细胞变性。
DOI：
10.1111/jcmm.16424
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发表时间：
2021-05
影响因子：
5.3
通讯作者：
Sun G
中科院分区：
文献类型：
--
作者：
Guo S;Su Q;Wen J;Zhu K;Tan J;Fu Q;Sun G
腰椎间盘氧化应激导致髓核（NP）退变。然而，这一过程的分子机制尚不清楚。在这项研究中，我们描述了一个关键的钙结合蛋白S100A9，它是由氧化应激诱导的，并在退行性NP中高度表达。免疫荧光染色和Western blotting显示，S100A9通过上调促凋亡标志物（cleaved caspase‐3、cytochrome c和Bax）的表达诱导NP细胞体外凋亡。此外，RT - PCR分析显示，S100A9的表达通过上调基质降解酶的表达导致NP基质降解，并通过上调细胞因子的表达增加炎症反应。因此，S100A9通过发挥促凋亡、促降解和促炎症作用诱导NP细胞变性。通过给予特异性NF - κB抑制剂SC75741，探讨了S100A9诱导NP变性的详细机制。我们得出结论，S100A9通过激活NF - κB信号通路诱导NP细胞凋亡，引起基质降解并放大炎症反应。抑制S100A9在NP中诱导的这些促凋亡、促降解和促炎症作用可能是减缓腰椎间盘退变的有利治疗策略。
Oxidative stress in the lumbar disc leads to the degeneration of nucleus pulposus (NP). However, the molecular mechanisms underlying this process remain unclear. In this study, we delineated a key calcium‐binding protein, S100A9, which was induced by oxidative stress and was highly expressed in the degenerative NP. Immunofluorescence staining and Western blotting revealed that S100A9 induced NP cell apoptosis in vitro by up‐regulating the expression of pro‐apoptotic markers, including cleaved caspase‐3, cytochrome c and Bax. Moreover, RT‐PCR analyses revealed that the expression of S100A9 caused NP matrix degradation by up‐regulating the expression of matrix degradation enzymes and increased the inflammatory response by up‐regulating cytokine expression. Therefore, S100A9 induced NP cell degeneration by exerting pro‐apoptotic, pro‐degradation and pro‐inflammatory effects. The detailed mechanism underlying S100A9‐induced NP degeneration was explored by administering SC75741, a specific NF‐κB inhibitor in vitro. We concluded that S100A9 induced NP cell apoptosis, caused matrix degradation and amplified the inflammatory response through the activation of the NF‐κB signalling pathway. Inhibition of these pro‐apoptotic, pro‐degradation and pro‐inflammatory effects induced by S100A9 in NP may be a favourable therapeutic strategy to slow lumbar disc degeneration.
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