The inflammatory cytokine TNF-α promotes the premature senescence of rat nucleus pulposus cells via the PI3K/Akt signaling pathway.
The inflammatory cytokine TNF-α promotes the premature senescence of rat nucleus pulposus cells via the PI3K/Akt signaling pathway.
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DOI：
10.1038/srep42938
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发表时间：
2017-02-17
影响因子：
4.6
通讯作者：
Zhou Q
中科院分区：
文献类型：
--
作者：
Li P;Gan Y;Xu Y;Song L;Wang L;Ouyang B;Zhang C;Zhou Q
髓核细胞过早衰老和炎症是椎间盘退变的两个共同特征。本研究探讨炎症细胞因子TNF-α对NP细胞过早衰老的影响及其分子机制。用不同浓度的TNF-α或不加TNF-α培养大鼠NP细胞1天和3天。使用抑制剂LY294002来确定PI3K/Akt通路的作用。NP细胞与TNF-α孵育3天后，在对照培养基中恢复3天，分析细胞衰老情况。结果表明，TNF-α促进NP细胞的过早衰老，表现为细胞增殖减少，端粒酶活性降低，SA-β-gal染色增加，停留在细胞周期G1期的细胞比例增加，基质蛋白合成能力减弱，衰老标志物p16和p53表达上调。此外，在实验第3天，高TNF-α浓度比低TNF-α浓度产生更大的效果。进一步分析表明，抑制PI3K/Akt通路可减轻TNF-α-诱导的NP细胞过早衰老。此外，TNF-α停用后，TNF-α诱导的NP细胞衰老未恢复。综上所述，TNF-α促进NP细胞过早衰老，PI3K/Akt通路的激活参与了这一过程。
Premature senescence of nucleus pulposus (NP) cells and inflammation are two common features of degenerated discs. This study investigated the effects of the inflammatory cytokine TNF-α on the premature senescence of NP cells and the molecular mechanism behind this process. Rat NP cells were cultured with or without different concentrations of TNF-α for 1 and 3 days. The inhibitor LY294002 was used to determine the role of the PI3K/Akt pathway. NP cells that were incubated with TNF-α for 3 days followed by 3 days of recovery in the control medium were used to analyze cellular senescence. Results showed that TNF-α promoted premature senescence of NP cells, as indicated by decreased cell proliferation, decreased telomerase activity, increased SA-β-gal staining, the fraction of cells arrested in the G1 phase of the cell cycle, the attenuated ability to synthesize matrix proteins and the up-regulated expression of the senescence marker p16 and p53. Moreover, a high TNF-α concentration produced greater effects than a low TNF-α concentration on day 3 of the experiment. Further analysis indicated that the inhibition of the PI3K/Akt pathway attenuated the TNF-α-induced premature senescence of NP cells. Additionally, TNF-α-induced NP cell senescence did not recover after TNF-α was withdrawn. In conclusion, TNF-α promotes the premature senescence of NP cells, and activation of the PI3K/Akt pathway is involved in this process.