Document Detail

Mitochondrial dysfunction in osteoarthritis is associated with down-regulation of superoxide dismutase 2.
MedLine Citation:
PMID:  23138846     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Superoxide dismutase 2 (SOD2) is down- regulated in osteoarthritis (OA). This study was undertaken to investigate the functional effects of this down-regulation in the context of oxidative damage and mitochondrial dysfunction.
METHODS: Lipid peroxidation in articular cartilage from OA patients and from lesion-free control subjects with femoral neck fracture was assessed by measuring malondialdehyde levels using the thiobarbituric acid reactive substances assay. Long-range polymerase chain reaction amplification and a mitochondrial DNA (mtDNA) strand break assay were used to investigate the presence of somatic large-scale mtDNA rearrangements in cartilage. Microscale oxygraphy was used to explore possible changes in mitochondrial respiratory activity between OA and control chondrocytes. RNA interference was used to determine the effects of SOD2 depletion on lipid peroxidation, mtDNA damage, and mitochondrial respiration.
RESULTS: OA cartilage had higher levels of lipid peroxidation compared to control cartilage, and lipid peroxidation was similarly elevated in SOD2-depleted chondrocytes. SOD2 depletion led to a significant increase in mtDNA strand breaks in chondrocytes, but there was no notable difference in the level of strand breaks between OA and control chondrocytes. Furthermore, only very low levels of somatic, large-scale mtDNA rearrangements were identified in OA cartilage. OA chondrocytes showed less spare respiratory capacity (SRC) and higher proton leak compared to control chondrocytes. SOD2-depleted chondrocytes also showed less SRC and higher proton leak.
CONCLUSION: This is the first study to analyze the effects of SOD2 depletion in human articular chondrocytes in terms of changes to oxidation and mitochondrial function. The findings indicate that SOD2 depletion in chondrocytes leads to oxidative damage and mitochondrial dysfunction, suggesting that SOD2 down-regulation is a potential contributor to the pathogenesis of OA.
Christos Gavriilidis; Satomi Miwa; Thomas von Zglinicki; Robert W Taylor; David A Young
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  65     ISSN:  1529-0131     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-29     Completed Date:  2013-04-11     Revised Date:  2014-02-24    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  378-87     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2013 by the American College of Rheumatology.
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MeSH Terms
Cartilage, Articular / enzymology*
Cells, Cultured
Chondrocytes / enzymology
Lipid Peroxidation
Mitochondria / enzymology*,  genetics
Osteoarthritis / enzymology*,  genetics
Reactive Oxygen Species / metabolism
Superoxide Dismutase / genetics,  metabolism*
Grant Support
096919//Wellcome Trust; 18261//Arthritis Research UK; BB/I020748/1//Biotechnology and Biological Sciences Research Council; G0601333//Medical Research Council
Reg. No./Substance:
0/Reactive Oxygen Species; EC Dismutase; EC dismutase 2

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