title: SIRT1 alleviates senescence of degenerative human intervertebral disc cartilage endo-plate cells via the p53/p21 pathway.
abstract: Cartilage end plates (CEP) degeneration plays an integral role in intervertebral disc (IVD) degeneration resulting from nutrient diffusion disorders. Although cell senescence resulting from oxidative stress is known to contribute to degeneration, no studies concerning the role of senescence in CEP degeneration have been conducted. SIRT1 is a longevity gene that plays a pivotal role in many cellular functions, including cell senescence. Therefore, the aim of this study was to investigate whether senescence is more prominent in human degenerative CEP and whether SIRT1-regulated CEP cells senescence in degenerative IVD as well as identify the signaling pathways that control that cell fate decision. In this study, the cell senescence phenotype was found to be more prominent in the CEP cells obtained from disc degenerative disease (DDD) patients than in the CEP cells obtained from age-matched lumbar vertebral fractures (LVF) patients. In addition, the results indicated that p53/p21 pathway plays an important role in the senescence of CEP cells in vivo and vitro. Furthermore, SIRT1 was found to be capable of alleviating the oxidative stress-induced senescence of CEP cells in humans via p53/p21 pathway. Thus, the information presented in this study could be used to further investigate the underlying mechanisms of CEP.
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Nian
authors.initials: N
authors.lastname: Zhou
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Dong
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Liangbo
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Quanhe
authors.initials: Q
authors.lastname: Qiu
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Jieliang
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Song
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hao
authors.affiliation: Department of Rehabilitation Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Dawu
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Zhenming
authors.initials: Z
authors.lastname: Hu
mesh_terms: D000328:Adult; D002356:Cartilage / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D016922:Cellular Senescence; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005260:Female; D050724:Fractures, Cartilage / Q000378:metabolism*; D006801:Humans; D055959:Intervertebral Disc Degeneration / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53; C447939:SIRT1 protein, human; D056564:Sirtuin 1