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. 2018 Nov 13;38(6):BSR20181451.
doi: 10.1042/BSR20181451. Print 2018 Dec 21.

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

Jiabin Fu  1   2 , Wei Yu  2 , Dianming Jiang  3
Affiliations

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

Jiabin Fu et al. Biosci Rep. .

Retraction in

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: The present 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 severe degenerative disc promotes NP cell senescence through regulating the p38 MAPK pathway. The present study provides a new mechanism that drives NP cell senescence during disc degeneration.

Keywords: intervertebral disc; nucleus pulposus; p38 MAPK; pH; senescence.

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Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1
Figure 1. Cell proliferation potency of NP cells
(A) CCK-8 assay. (B) EdU incorporation assay. Data are expressed as mean ± S.D. (n=3). *: Shows a statistical difference (P<0.05) between two groups.
Figure 2
Figure 2. Cell cycle analysis of NP cells
The histogram shows cell fraction proportion of each cell cycle (G0/G1, S, and G2/M).
Figure 3
Figure 3. Telomerase activity of NP cells
Data are expressed as mean ± S.D. (n=3). *: Shows a statistical difference (P<0.05) between two groups.
Figure 4
Figure 4. Analysis of the expression of senescence-related molecules (p16 and p53) in NP cells
(A) Real-time PCR analysis. (B) Western blot analysis. Data are expressed as mean ± S.D. (n=3). *: Shows a statistical difference (P<0.05) between two groups.
Figure 5
Figure 5. Analysis of the expression of matrix molecules (aggrecan and collagen II) in NP cells
(A) Real-time PCR analysis. (B) Western blot analysis. Data are expressed as mean ± S.D. (n=3). *: Shows a statistical difference (P<0.05) between two groups.
Figure 6
Figure 6. Analysis of activity of the p38 MAPK pathway in NP cells
Data are expressed as mean ± S.D. (n=3). *: Shows a statistical difference (P<0.05) between two groups.
See this image and copyright information in PMC

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