SOD2 orchestrates redox homeostasis in intervertebral discs : A novel insight into oxidative stress-mediated degeneration and therapeutic potential
Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved..
Low back pain (LBP) is a pervasive global health concern, primarily associated with intervertebral disc (IVD) degeneration. Although oxidative stress has been shown to contribute to IVD degeneration, the underlying mechanisms remain undetermined. This study aimed to unravel the role of superoxide dismutase 2 (SOD2) in IVD pathogenesis and target oxidative stress to limit IVD degeneration. SOD2 demonstrated a dynamic regulation in surgically excised human IVD tissues, with initial upregulation in moderate degeneration and downregulation in severely degenerated IVDs. Through a comprehensive set of in vitro and in vivo experiments, we found a suggestive association between excessive mitochondrial superoxide, cellular senescence, and matrix degradation in human and mouse IVD cells. We confirmed that aging and mechanical stress, established triggers for IVD degeneration, escalated mitochondrial superoxide levels in mouse models. Critically, chondrocyte-specific Sod2 deficiency accelerated age-related and mechanical stress-induced disc degeneration in mice, and could be attenuated by β-nicotinamide mononucleotide treatment. These revelations underscore the central role of SOD2 in IVD redox balance and unveil potential therapeutic avenues, making SOD2 and mitochondrial superoxide promising targets for effective LBP interventions.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:71 |
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| Enthalten in: |
Redox biology - 71(2024) vom: 26. Apr., Seite 103091 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tamagawa, Shota [VerfasserIn] |
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| Links: |
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| Themen: |
11062-77-4 |
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| Anmerkungen: |
Date Completed 01.04.2024 Date Revised 01.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.redox.2024.103091 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369027302 |
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| 520 | |a Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a Low back pain (LBP) is a pervasive global health concern, primarily associated with intervertebral disc (IVD) degeneration. Although oxidative stress has been shown to contribute to IVD degeneration, the underlying mechanisms remain undetermined. This study aimed to unravel the role of superoxide dismutase 2 (SOD2) in IVD pathogenesis and target oxidative stress to limit IVD degeneration. SOD2 demonstrated a dynamic regulation in surgically excised human IVD tissues, with initial upregulation in moderate degeneration and downregulation in severely degenerated IVDs. Through a comprehensive set of in vitro and in vivo experiments, we found a suggestive association between excessive mitochondrial superoxide, cellular senescence, and matrix degradation in human and mouse IVD cells. We confirmed that aging and mechanical stress, established triggers for IVD degeneration, escalated mitochondrial superoxide levels in mouse models. Critically, chondrocyte-specific Sod2 deficiency accelerated age-related and mechanical stress-induced disc degeneration in mice, and could be attenuated by β-nicotinamide mononucleotide treatment. These revelations underscore the central role of SOD2 in IVD redox balance and unveil potential therapeutic avenues, making SOD2 and mitochondrial superoxide promising targets for effective LBP interventions | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Aging | |
| 650 | 4 | |a Intervertebral disc degeneration | |
| 650 | 4 | |a Low back pain | |
| 650 | 4 | |a Mechanical stress | |
| 650 | 4 | |a Oxidative stress | |
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| 700 | 1 | |a Nakamura, Yoshihiko |e verfasserin |4 aut | |
| 700 | 1 | |a Warita, Takayuki |e verfasserin |4 aut | |
| 700 | 1 | |a Matsushita, Erika |e verfasserin |4 aut | |
| 700 | 1 | |a Schol, Jordy |e verfasserin |4 aut | |
| 700 | 1 | |a Soma, Hazuki |e verfasserin |4 aut | |
| 700 | 1 | |a Ogasawara, Shota |e verfasserin |4 aut | |
| 700 | 1 | |a Munesada, Daiki |e verfasserin |4 aut | |
| 700 | 1 | |a Koike, Masato |e verfasserin |4 aut | |
| 700 | 1 | |a Shimizu, Takahiko |e verfasserin |4 aut | |
| 700 | 1 | |a Sato, Masato |e verfasserin |4 aut | |
| 700 | 1 | |a Ishijima, Muneaki |e verfasserin |4 aut | |
| 700 | 1 | |a Watanabe, Masahiko |e verfasserin |4 aut | |
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