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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BMC
2017-09-01
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Series: | Arthritis Research & Therapy |
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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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issn | 1478-6362 |
language | English |
last_indexed | 2024-12-10T10:32:56Z |
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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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