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

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 proce...

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Main Authors: Pei Li, Gang Hou, Ruijie Zhang, Yibo Gan, Yuan Xu, Lei Song, Qiang Zhou
Format: Article
Language:English
Published: BMC 2017-09-01
Series:Arthritis Research & Therapy
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13075-017-1384-z
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author Pei Li
Gang Hou
Ruijie Zhang
Yibo Gan
Yuan Xu
Lei Song
Qiang Zhou
author_facet Pei Li
Gang Hou
Ruijie Zhang
Yibo Gan
Yuan Xu
Lei Song
Qiang Zhou
author_sort Pei Li
collection DOAJ
description 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.
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spelling doaj.art-dd4b5b3ed9344c5ba8aef935eca9b14a2022-12-22T01:52:31ZengBMCArthritis Research & Therapy1478-63622017-09-0119111410.1186/s13075-017-1384-zHigh-magnitude compression accelerates the premature senescence of nucleus pulposus cells via the p38 MAPK-ROS pathwayPei Li0Gang Hou1Ruijie Zhang2Yibo Gan3Yuan Xu4Lei Song5Qiang Zhou6Department of Orthopaedic SurgeryDepartment of Orthopaedics, Third Affiliated Hospital of Sun Yat-sen UniversityDepartment of Respiratory Medicine, the Third Xiangya Hospital, Central South UniversityDepartment of Orthopaedic Surgery, Southwest Hospital, Third Military Medical UniversityDepartment of Orthopaedic Surgery, Xinqiao Hospital, Third Military Medical UniversityDepartment of Orthopaedic Surgery, Southwest Hospital, Third Military Medical UniversityDepartment of Orthopaedic Surgery, Southwest Hospital, Third Military Medical UniversityAbstract 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.http://link.springer.com/article/10.1186/s13075-017-1384-zCompressionSenescenceNucleus pulposus cellp38 MAPKReactive oxygen species
spellingShingle Pei Li
Gang Hou
Ruijie Zhang
Yibo Gan
Yuan Xu
Lei Song
Qiang Zhou
High-magnitude compression accelerates the premature senescence of nucleus pulposus cells via the p38 MAPK-ROS pathway
Arthritis Research & Therapy
Compression
Senescence
Nucleus pulposus cell
p38 MAPK
Reactive oxygen species
title High-magnitude compression accelerates the premature senescence of nucleus pulposus cells via the p38 MAPK-ROS pathway
title_full High-magnitude compression accelerates the premature senescence of nucleus pulposus cells via the p38 MAPK-ROS pathway
title_fullStr High-magnitude compression accelerates the premature senescence of nucleus pulposus cells via the p38 MAPK-ROS pathway
title_full_unstemmed High-magnitude compression accelerates the premature senescence of nucleus pulposus cells via the p38 MAPK-ROS pathway
title_short High-magnitude compression accelerates the premature senescence of nucleus pulposus cells via the p38 MAPK-ROS pathway
title_sort high magnitude compression accelerates the premature senescence of nucleus pulposus cells via the p38 mapk ros pathway
topic Compression
Senescence
Nucleus pulposus cell
p38 MAPK
Reactive oxygen species
url http://link.springer.com/article/10.1186/s13075-017-1384-z
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