title: The inflammatory cytokine TNF-α 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-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 Additionally, TNF-α-induced NP cell senescence did not recover after TNF-α was withdrawn.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.
authors.affiliation: Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Yibo
authors.initials: Y
authors.lastname: Gan
authors.affiliation: Department of Orthopedic Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Liyuan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Ouyang
authors.affiliation: Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Chengmin
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D053674:Aggrecans / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D024043:Collagen Type II / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D008297:Male; D000070614:Nucleus Pulposus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D053674:Aggrecans; D024043:Collagen Type II; D019941:Cyclin-Dependent Kinase Inhibitor p16; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt