P16 deficiency attenuates intervertebral disc degeneration by adjusting oxidative stress and nucleus pulposus cell cycle

Abstract: The cell cycle regulator p16 is known as a biomarker and an effector of aging. However, its function in intervertebral disc degeneration (IVDD) is unclear. In this study, p16 expression levels were found to be positively correlated with the severity of human IVDD. In a mouse tail suspension (TS)-induced IVDD model, lumbar intervertebral disc height index and matrix protein expression levels were reduced significantly were largely rescued by p16 deletion. In TS mouse discs, reactive oxygen species levels, proportions of senescent cells, and the senescence-associated secretory phenotype (SASP) were all increased, cell cycling was delayed, and expression was downregulated for Sirt1, superoxide dismutase 1/2, cyclin-dependent kinases 4/6, phosphorylated retinoblastoma protein, and transcription factor E2F1/2. However, these effects were rescued by p16 deletion. Our results demonstrate that p16 plays an important role in IVDD pathogenesis and that its deletion attenuates IVDD by promoting cell cycle and inhibiting SASP, cell senescence, and oxidative stress.

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: eLife. - 9 (2020) , ISSN: 2050-084X

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2020
• Creator: Che, Hui ; Li, Jie ; Li, You ; Ma, Cheng ; Liu, Huan ; Qin, Jingyi ; Dong, Jianghui ; Zhang, Zhen ; Xian, Cory J. ; Miao, Dengshun ; Wang, Liping ; Ren, Yongxin

Further information

• DOI: 10.7554/eLife.52570
• URN: urn:nbn:de:bsz:25-freidok-1668064
• Rights: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 13.01.2023, 11:53 AM CET