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p16 deficiency attenuates intervertebral disc degeneration by adjusting oxidative stress and nucleus pulposus cell cycle

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)-ind...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065909/
https://www.ncbi.nlm.nih.gov/pubmed/32125276
http://dx.doi.org/10.7554/eLife.52570
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author 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
author_facet 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
author_sort Che, Hui
collection PubMed
description 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.
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spelling pubmed-70659092020-03-12 p16 deficiency attenuates intervertebral disc degeneration by adjusting oxidative stress and nucleus pulposus cell cycle 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 eLife Human Biology and Medicine 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. eLife Sciences Publications, Ltd 2020-03-03 /pmc/articles/PMC7065909/ /pubmed/32125276 http://dx.doi.org/10.7554/eLife.52570 Text en © 2020, Che et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Human Biology and Medicine
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
p16 deficiency attenuates intervertebral disc degeneration by adjusting oxidative stress and nucleus pulposus cell cycle
title p16 deficiency attenuates intervertebral disc degeneration by adjusting oxidative stress and nucleus pulposus cell cycle
title_full p16 deficiency attenuates intervertebral disc degeneration by adjusting oxidative stress and nucleus pulposus cell cycle
title_fullStr p16 deficiency attenuates intervertebral disc degeneration by adjusting oxidative stress and nucleus pulposus cell cycle
title_full_unstemmed p16 deficiency attenuates intervertebral disc degeneration by adjusting oxidative stress and nucleus pulposus cell cycle
title_short p16 deficiency attenuates intervertebral disc degeneration by adjusting oxidative stress and nucleus pulposus cell cycle
title_sort p16 deficiency attenuates intervertebral disc degeneration by adjusting oxidative stress and nucleus pulposus cell cycle
topic Human Biology and Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065909/
https://www.ncbi.nlm.nih.gov/pubmed/32125276
http://dx.doi.org/10.7554/eLife.52570
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