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

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 was withdrawn.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

SUBMITTER: Li P 

PROVIDER: S-EPMC5314336 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature