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

Mitchell C Coleman; Marc J Brouillette; Nicholas S Andresen; Rebecca E Oberley-Deegan; James M Martin

doi:10.3390/antiox6040098

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

Journal article

Open access

Peer reviewed

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

Mitchell C Coleman, Marc J Brouillette, Nicholas S Andresen, Rebecca E Oberley-Deegan and James M Martin

Antioxidants, Vol.6(4), p.98

12/01/2017

DOI: 10.3390/antiox6040098

PMCID: PMC5745508

PMID: 29189731

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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.

Trauma

Arthritis

superoxide

superoxide dismutase (SOD)

mitochondria

cartilage

Details

Title: Subtitle: Differential Effects of Superoxide Dismutase Mimetics after Mechanical Overload of Articular Cartilage
Creators: Mitchell C Coleman - Department of Orthopedics and Rehabilitation, University of Iowa, Iowa City, IA 52242, USA
Marc J Brouillette - Department of Orthopedics and Rehabilitation, University of Iowa, Iowa City, IA 52242, USA
Nicholas S Andresen - Department of Orthopedics and Rehabilitation, University of Iowa, Iowa City, IA 52242, USA
Rebecca E Oberley-Deegan - Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
James M Martin - Department of Orthopedics and Rehabilitation, University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Antioxidants, Vol.6(4), p.98
DOI: 10.3390/antiox6040098
PMID: 29189731
PMCID: PMC5745508
NLM abbreviation: Antioxidants (Basel)
ISSN: 2076-3921
eISSN: 2076-3921
Publisher: MDPI
Grant note: DOI: 10.13039/100007683, name: NIH, award: CORT 5 P50 AR055533-05, K99 AR070914; DOI: 10.13039/100000005, name: Department of Defense, award: W81XWH-11-1-0583
Language: English
Date published: 12/01/2017
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Radiation Oncology
Record Identifier: 9984040266602771

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