p16 deficiency attenuates intervertebral disc degeneration by adjusting oxidative stress and nucleus pulposus cell cycle
- The First Affiliated Hospital of Nanjing Medical University, China
- Xuzhou Central Hospital, China
- Chinese Academy of Sciences, China
- University of South Australia, Australia
- Nanjing Medical University, China
Abstract
Cell cycle regulator p16 is known 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 positively correlated with 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 senescence-associated secretory phenotype (SASP) were 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 cycling and inhibiting SASP, cell senescence, and oxidative stress.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Funding
National Health and Medical Research Council (1158402)
- Liping Wang
National Natural Science Foundation of China (81572149)
- Dengshun Miao
- Yongxin Ren
China Scholarship Council (CSC201908080215)
- Hui Che
National Natural Science Foundation of China (81671928)
- Cory J Xian
- Liping Wang
National Health and Medical Research Council (1127396)
- Cory J Xian
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal use was approved by the Institutional Animal Care and Use Committee of Nanjing Medical University (approval number: IACUC-1709021).
Human subjects: This work was implemented by the approval of the Ethics Committee of The First Affiliated Hospital of Nanjing Medical University (approval number: 2018-SR-233). Before the operation, the informed consents of the patients have been obtained, including the patient's voluntary donation of the diseased nucleus pulposus tissue extracted from the operation, and their consents that all specimens will be used for scientific research and the results obtained will be published in scientific journals.
Copyright
© 2020, Che et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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p16 deficiency attenuates intervertebral disc degeneration by adjusting oxidative stress and nucleus pulposus cell cycle
eLife 9:e52570.
https://doi.org/10.7554/eLife.52570
