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Antioxidants 2017, 6(4), 98; doi:10.3390/antiox6040098

Differential Effects of Superoxide Dismutase Mimetics after Mechanical Overload of Articular Cartilage

1
Department of Orthopedics and Rehabilitation, University of Iowa, Iowa City, IA 52242, USA
2
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
*
Author to whom correspondence should be addressed.
Received: 19 October 2017 / Revised: 20 November 2017 / Accepted: 28 November 2017 / Published: 30 November 2017
(This article belongs to the Special Issue Superoxide Dismutase (SOD) Enzymes, Mimetics and Oxygen Radicals)
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Abstract

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. View Full-Text
Keywords: superoxide; superoxide dismutase (SOD); arthritis; trauma; mitochondria; cartilage superoxide; superoxide dismutase (SOD); arthritis; trauma; mitochondria; cartilage
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MDPI and ACS Style

Coleman, M.C.; Brouillette, M.J.; Andresen, N.S.; Oberley-Deegan, R.E.; Martin, J.M. Differential Effects of Superoxide Dismutase Mimetics after Mechanical Overload of Articular Cartilage. Antioxidants 2017, 6, 98.

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