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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...

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Autores principales: Coleman, Mitchell C., Brouillette, Marc J., Andresen, Nicholas S., Oberley-Deegan, Rebecca E., Martin, James M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
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.
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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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