The inflammatory cytokine TNF-α promotes the premature senescence of rat nucleus pulposus cells via the PI3K/Akt signaling pathway

被引：99

作者：

Li, Pei ^{[1
]}

Gan, Yibo ^{[1
]}

Xu, Yuan ^{[2
]}

Song, Lei ^{[1
]}

Wang, Liyuan ^{[1
]}

Ouyang, Bin ^{[1
]}

Zhang, Chengmin ^{[1
]}

Zhou, Qiang ^{[1
]}

机构：

[1] Third Mil Med Univ, Southwest Hosp, Dept Orthoped Surg, Chongqing 400038, Peoples R China

[2] Third Mil Med Univ, Xinqiao Hosp, Dept Orthoped Surg, Chongqing 400037, Peoples R China

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

关键词：

VITRO LIFE-SPAN; NF-KAPPA-B; INTERVERTEBRAL DISC; IN-VITRO; CELLULAR SENESCENCE; OXIDATIVE STRESS; APOPTOSIS; PROLIFERATION; EXPRESSION; INTERLEUKIN-1-BETA;

D O I：

10.1038/srep42938

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-alpha 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-alpha 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-alpha for 3 days followed by 3 days of recovery in the control medium were used to analyze cellular senescence. Results showed that TNF-alpha promoted premature senescence of NP cells, as indicated by decreased cell proliferation, decreased telomerase activity, increased SA-beta-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-alpha concentration produced greater effects than a low TNF-alpha concentration on day 3 of the experiment. Further analysis indicated that the inhibition of the PI3K/Akt pathway attenuated the TNF-alpha induced premature senescence of NP cells. Additionally, TNF-alpha-induced NP cell senescence did not recover after TNF-alpha was withdrawn. In conclusion, TNF-alpha promotes the premature senescence of NP cells, and activation of the PI3K/Akt pathway is involved in this process.

引用

页数：12

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