Aspirin-Mediated Attenuation of Intervertebral Disc Degeneration by Ameliorating Reactive Oxygen Species In Vivo and In Vitro
Intervertebral disc (IVD) degeneration (IDD) is a major cause of low back pain. The pathogenesis of IDD is associated with the disturbance of reactive oxygen species (ROS) equilibrium, inflammation, and matrix loss. Aspirin is a nonsteroidal anti-inflammatory drug that effectively inhibits inflammat...
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Series: | Oxidative Medicine and Cellular Longevity |
Online Access: | http://dx.doi.org/10.1155/2019/7189854 |
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doaj-39cd56697723409a9a2d47f8159e39d62020-11-25T01:34:37ZengHindawi LimitedOxidative Medicine and Cellular Longevity1942-09001942-09942019-01-01201910.1155/2019/71898547189854Aspirin-Mediated Attenuation of Intervertebral Disc Degeneration by Ameliorating Reactive Oxygen Species In Vivo and In VitroYu Liu0Jiayi Lin1Xiexing Wu2Xiaobin Guo3Houyi Sun4Binqing Yu5Jining Shen6Jiaxiang Bai7Zhanghuan Chen8Huilin Yang9Dechun Geng10Haiqing Mao11Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou 215006, ChinaDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou 215006, ChinaDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou 215006, ChinaDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou 215006, ChinaDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou 215006, ChinaDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou 215006, ChinaDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou 215006, ChinaDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou 215006, ChinaDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou 215006, ChinaDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou 215006, ChinaDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou 215006, ChinaDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou 215006, ChinaIntervertebral disc (IVD) degeneration (IDD) is a major cause of low back pain. The pathogenesis of IDD is associated with the disturbance of reactive oxygen species (ROS) equilibrium, inflammation, and matrix loss. Aspirin is a nonsteroidal anti-inflammatory drug that effectively inhibits inflammation and oxidative stress and has been widely used for the treatment of back pain. Therefore, we hypothesize that aspirin reverses the IDD process via antioxidative and anti-inflammatory effects on the AMPK signaling pathway. In vitro, aspirin diminished cellular oxygen free radicals (ROS, nitric oxide (NO)) and inflammatory cytokines (interleukin- (IL-) 1β and IL-6 and tumor necrosis factor alpha (TNF-α)) induced by lipopolysaccharides (LPS) in nucleus pulposus cells (NPCs). We found that aspirin preserved the extracellular matrix (ECM) content of collagen type II (COL2) and aggrecan while inhibiting the expression of matrix-degenerating enzymes, including matrix metalloproteinase 3 and 13 (MMP-3 and MMP-13) and A disintegrin and metalloproteinase with thrombospondin motifs 4 and 5 (ADAMTS-4, ADAMTS-5). Aspirin significantly promoted the ratios of p-AMPK to AMPK and p-ACC to ACC expression in NPCs. Furthermore, pretreatment with the AMPK inhibitor compound C abrogated the antioxidant effects of aspirin. In vivo, an IDD model was established in Sprague-Dawley rats via percutaneous disc puncture with the 20-gauge needle on levels 8-9 and 9-10 of the coccygeal vertebrae. Imaging assessment showed that after aspirin treatment, improvements in disc height index (DHI) ranged from 1.22-fold to 1.54-fold and nucleus pulposus signal strength improved from 1.26-fold to 1.33-fold. Histological analysis showed that aspirin treatment prevented the loss of COL2 and decreased MMP-3 and MMP-13, inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), IL-1β, and TNF-α expression in the IVD tissues. These results suggest that treatment with aspirin could reverse the IDD process via the AMPK signaling pathway, which provides new insights into the potential clinical applications of aspirin, particularly for IDD treatment.http://dx.doi.org/10.1155/2019/7189854 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yu Liu Jiayi Lin Xiexing Wu Xiaobin Guo Houyi Sun Binqing Yu Jining Shen Jiaxiang Bai Zhanghuan Chen Huilin Yang Dechun Geng Haiqing Mao |
spellingShingle |
Yu Liu Jiayi Lin Xiexing Wu Xiaobin Guo Houyi Sun Binqing Yu Jining Shen Jiaxiang Bai Zhanghuan Chen Huilin Yang Dechun Geng Haiqing Mao Aspirin-Mediated Attenuation of Intervertebral Disc Degeneration by Ameliorating Reactive Oxygen Species In Vivo and In Vitro Oxidative Medicine and Cellular Longevity |
author_facet |
Yu Liu Jiayi Lin Xiexing Wu Xiaobin Guo Houyi Sun Binqing Yu Jining Shen Jiaxiang Bai Zhanghuan Chen Huilin Yang Dechun Geng Haiqing Mao |
author_sort |
Yu Liu |
title |
Aspirin-Mediated Attenuation of Intervertebral Disc Degeneration by Ameliorating Reactive Oxygen Species In Vivo and In Vitro |
title_short |
Aspirin-Mediated Attenuation of Intervertebral Disc Degeneration by Ameliorating Reactive Oxygen Species In Vivo and In Vitro |
title_full |
Aspirin-Mediated Attenuation of Intervertebral Disc Degeneration by Ameliorating Reactive Oxygen Species In Vivo and In Vitro |
title_fullStr |
Aspirin-Mediated Attenuation of Intervertebral Disc Degeneration by Ameliorating Reactive Oxygen Species In Vivo and In Vitro |
title_full_unstemmed |
Aspirin-Mediated Attenuation of Intervertebral Disc Degeneration by Ameliorating Reactive Oxygen Species In Vivo and In Vitro |
title_sort |
aspirin-mediated attenuation of intervertebral disc degeneration by ameliorating reactive oxygen species in vivo and in vitro |
publisher |
Hindawi Limited |
series |
Oxidative Medicine and Cellular Longevity |
issn |
1942-0900 1942-0994 |
publishDate |
2019-01-01 |
description |
Intervertebral disc (IVD) degeneration (IDD) is a major cause of low back pain. The pathogenesis of IDD is associated with the disturbance of reactive oxygen species (ROS) equilibrium, inflammation, and matrix loss. Aspirin is a nonsteroidal anti-inflammatory drug that effectively inhibits inflammation and oxidative stress and has been widely used for the treatment of back pain. Therefore, we hypothesize that aspirin reverses the IDD process via antioxidative and anti-inflammatory effects on the AMPK signaling pathway. In vitro, aspirin diminished cellular oxygen free radicals (ROS, nitric oxide (NO)) and inflammatory cytokines (interleukin- (IL-) 1β and IL-6 and tumor necrosis factor alpha (TNF-α)) induced by lipopolysaccharides (LPS) in nucleus pulposus cells (NPCs). We found that aspirin preserved the extracellular matrix (ECM) content of collagen type II (COL2) and aggrecan while inhibiting the expression of matrix-degenerating enzymes, including matrix metalloproteinase 3 and 13 (MMP-3 and MMP-13) and A disintegrin and metalloproteinase with thrombospondin motifs 4 and 5 (ADAMTS-4, ADAMTS-5). Aspirin significantly promoted the ratios of p-AMPK to AMPK and p-ACC to ACC expression in NPCs. Furthermore, pretreatment with the AMPK inhibitor compound C abrogated the antioxidant effects of aspirin. In vivo, an IDD model was established in Sprague-Dawley rats via percutaneous disc puncture with the 20-gauge needle on levels 8-9 and 9-10 of the coccygeal vertebrae. Imaging assessment showed that after aspirin treatment, improvements in disc height index (DHI) ranged from 1.22-fold to 1.54-fold and nucleus pulposus signal strength improved from 1.26-fold to 1.33-fold. Histological analysis showed that aspirin treatment prevented the loss of COL2 and decreased MMP-3 and MMP-13, inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), IL-1β, and TNF-α expression in the IVD tissues. These results suggest that treatment with aspirin could reverse the IDD process via the AMPK signaling pathway, which provides new insights into the potential clinical applications of aspirin, particularly for IDD treatment. |
url |
http://dx.doi.org/10.1155/2019/7189854 |
work_keys_str_mv |
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