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Differential Effects of Superoxide Dismutase Mimetics after Mechanical Overload of Articular Cartilage
Post-traumatic osteoarthritis can develop as a result of the initial mechanical impact causing the injury and also as a result of chronic changes in mechanical loading of the joint. Aberrant mechanical loading initiates excessive production of reactive oxygen species, oxidative damage, and stress th...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745508/ https://www.ncbi.nlm.nih.gov/pubmed/29189731 http://dx.doi.org/10.3390/antiox6040098 |
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author | Coleman, Mitchell C. Brouillette, Marc J. Andresen, Nicholas S. Oberley-Deegan, Rebecca E. Martin, James M. |
author_facet | Coleman, Mitchell C. Brouillette, Marc J. Andresen, Nicholas S. Oberley-Deegan, Rebecca E. Martin, James M. |
author_sort | Coleman, Mitchell C. |
collection | PubMed |
description | Post-traumatic osteoarthritis can develop as a result of the initial mechanical impact causing the injury and also as a result of chronic changes in mechanical loading of the joint. Aberrant mechanical loading initiates excessive production of reactive oxygen species, oxidative damage, and stress that appears to damage mitochondria in the surviving chondrocytes. To probe the benefits of increasing superoxide removal with small molecular weight superoxide dismutase mimetics under severe loads, we applied both impact and overload injury scenarios to bovine osteochondral explants using characterized mechanical platforms with and without GC4403, MnTE-2-PyP, and MnTnBuOE-2-PyP. In impact scenarios, each of these mimetics provides some dose-dependent protection from cell death and loss of mitochondrial content while in repeated overloading scenarios only MnTnBuOE-2-PyP provided a clear benefit to chondrocytes. These results support the hypothesis that superoxide is generated in excess after impact injuries and suggest that superoxide production within the lipid compartment may be a critical mediator of responses to chronic overload. This is an important nuance distinguishing roles of superoxide, and thus superoxide dismutases, in mediating damage to cellular machinery in hyper-acute impact scenarios compared to chronic scenarios. |
format | Online Article Text |
id | pubmed-5745508 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-57455082018-01-02 Differential Effects of Superoxide Dismutase Mimetics after Mechanical Overload of Articular Cartilage Coleman, Mitchell C. Brouillette, Marc J. Andresen, Nicholas S. Oberley-Deegan, Rebecca E. Martin, James M. Antioxidants (Basel) Article Post-traumatic osteoarthritis can develop as a result of the initial mechanical impact causing the injury and also as a result of chronic changes in mechanical loading of the joint. Aberrant mechanical loading initiates excessive production of reactive oxygen species, oxidative damage, and stress that appears to damage mitochondria in the surviving chondrocytes. To probe the benefits of increasing superoxide removal with small molecular weight superoxide dismutase mimetics under severe loads, we applied both impact and overload injury scenarios to bovine osteochondral explants using characterized mechanical platforms with and without GC4403, MnTE-2-PyP, and MnTnBuOE-2-PyP. In impact scenarios, each of these mimetics provides some dose-dependent protection from cell death and loss of mitochondrial content while in repeated overloading scenarios only MnTnBuOE-2-PyP provided a clear benefit to chondrocytes. These results support the hypothesis that superoxide is generated in excess after impact injuries and suggest that superoxide production within the lipid compartment may be a critical mediator of responses to chronic overload. This is an important nuance distinguishing roles of superoxide, and thus superoxide dismutases, in mediating damage to cellular machinery in hyper-acute impact scenarios compared to chronic scenarios. MDPI 2017-11-30 /pmc/articles/PMC5745508/ /pubmed/29189731 http://dx.doi.org/10.3390/antiox6040098 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Coleman, Mitchell C. Brouillette, Marc J. Andresen, Nicholas S. Oberley-Deegan, Rebecca E. Martin, James M. Differential Effects of Superoxide Dismutase Mimetics after Mechanical Overload of Articular Cartilage |
title | Differential Effects of Superoxide Dismutase Mimetics after Mechanical Overload of Articular Cartilage |
title_full | Differential Effects of Superoxide Dismutase Mimetics after Mechanical Overload of Articular Cartilage |
title_fullStr | Differential Effects of Superoxide Dismutase Mimetics after Mechanical Overload of Articular Cartilage |
title_full_unstemmed | Differential Effects of Superoxide Dismutase Mimetics after Mechanical Overload of Articular Cartilage |
title_short | Differential Effects of Superoxide Dismutase Mimetics after Mechanical Overload of Articular Cartilage |
title_sort | differential effects of superoxide dismutase mimetics after mechanical overload of articular cartilage |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745508/ https://www.ncbi.nlm.nih.gov/pubmed/29189731 http://dx.doi.org/10.3390/antiox6040098 |
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