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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 1/2017

Open Access 01-12-2017 | Research article

High-magnitude compression accelerates the premature senescence of nucleus pulposus cells via the p38 MAPK-ROS pathway

Authors: Pei Li, Gang Hou, Ruijie Zhang, Yibo Gan, Yuan Xu, Lei Song, Qiang Zhou

Published in: Arthritis Research & Therapy | Issue 1/2017

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Abstract

Background

Mechanical overloading can lead to disc degeneration. Nucleus pulposus (NP) cell senescence is aggravated within the degenerated disc. This study was designed to investigate the effects of high compression on NP cell senescence and the underlying molecular mechanism of this process.

Methods

Rat NP cells seeded in decalcified bone matrix were subjected to non-compression (control) or compression (2% or 20% deformation, 1.0 Hz, 6 hours/day). The reactive oxygen species (ROS) scavenger N-acetylcysteine (NAC) and the p38 MAPK inhibitor SB203580 were used to investigate the roles of the ROS and p38 MAPK pathway under high-magnitude compression. Additionally, we studied the effects of compression (0.1 or 1.3 MPa, 1.0 Hz, 6 hours/day) in a rat disc organ culture.

Results

Both in scaffold and organ cultures, high-magnitude compression (20% deformation or 1.3 MPa) increased senescence-associated β-galactosidase (SA-β-Gal) activity, senescence marker (p16 and p53) expression, G1 cell cycle arrest, and ROS generation, and decreased cell proliferation, telomerase activity and matrix (aggrecan and collagen II) synthesis. Further analysis of the 20% deformation group showed that NAC inhibited NP cell senescence but had no obvious effect on phospho-p38 MAPK expression and that SB203580 significantly attenuated ROS generation and NP cell senescence.

Conclusions

High-magnitude compression can accelerate NP cell senescence through the p38 MAPK-ROS pathway.
Appendix
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Metadata
Title
High-magnitude compression accelerates the premature senescence of nucleus pulposus cells via the p38 MAPK-ROS pathway
Authors
Pei Li
Gang Hou
Ruijie Zhang
Yibo Gan
Yuan Xu
Lei Song
Qiang Zhou
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2017
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-017-1384-z

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