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Accepted Manuscript

Acidic pH promotes nucleus pulposus cell senescence through activating the p38 MPAK pathway

Jinbin Fu, Wei Yu, Dianming Jiang
Bioscience Reports Oct 05, 2018, BSR20181451; DOI: 10.1042/BSR20181451
Jinbin Fu
Chongqing Medical University, Chongqing, China
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Wei Yu
Chongqing Medical University, Chongqing, China
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Dianming Jiang
Chongqing Medical University, Chongqing, China
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  • For correspondence: jiangdm0822@sina.com
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Abstract

Background: Nucleus pulposus (NP) cell senescence is an important cellular feature within the degenerative disc. It is known that a very acidic niche exists in the degenerative disc, which participates in regulating disc cell viability and matrix metabolism. Objective: This study was aimed to investigate the role and potential signaling transduction pathway of an acidic pH in regulating NP cell senescence. Methods: Rat NP cells were cultured in an acidic pH of 7.2 close to that in a healthy disc (Control group) or in an acidic pH of 6.2 close to that in a severe degenerative disc (Experiment group) for 10 days. Additionally, the experimental NP cells were incubated along with the inhibitor SB203580 to analyze the role of p38 MAPK pathway in this process. Results: Compared with the control NP cells, experimental NP cells showed a suppressed cell proliferation potency, an increased G0/G1 phase fraction whereas a decreased S phase fraction and a declined telomerase activity, an up-regulated expression of senescence-related molecules (p16 and p53), and a down-regulated expression of matrix-related moleucles (aggrecan and collagen II). Further analysis showed that inhibition of the p38 MAPK pathway partly reversed effects of acidic pH of 6.2 on the experimental NP cells. Conclusion: The very acidic niche identified in a sever degenerative disc promotes NP cell senescence through regulating the p38 MAPK pathway. This study provides a new mechanism that drives NP cell senescence during disc degeneration.

  • intervertebral disc
  • nucleus pulposus
  • senescence
  • pH
  • p38 MAPK
  • ©2018 The Author(s)

This is an Accepted Manuscript; not the final Version of Record. You are encouraged to use the final Version of Record that, when published, will replace this manuscript and be freely available under a Creative Commons licence.

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Acidic pH promotes nucleus pulposus cell senescence through activating the p38 MPAK pathway
Jinbin Fu, Wei Yu, Dianming Jiang
Bioscience Reports Oct 2018, BSR20181451; DOI: 10.1042/BSR20181451
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Acidic pH promotes nucleus pulposus cell senescence through activating the p38 MPAK pathway
Jinbin Fu, Wei Yu, Dianming Jiang
Bioscience Reports Oct 2018, BSR20181451; DOI: 10.1042/BSR20181451

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Keywords

intervertebral disc
nucleus pulposus
senescence
pH
p38 MAPK

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