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Mitochondrial dysfunction in osteoarthritis is associated with down-regulation of superoxide dismutase 2†
Article first published online: 28 JAN 2013
Copyright © 2013 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 65, Issue 2, pages 378–387, February 2013
How to Cite
Gavriilidis, C., Miwa, S., von Zglinicki, T., Taylor, R. W. and Young, D. A. (2013), Mitochondrial dysfunction in osteoarthritis is associated with down-regulation of superoxide dismutase 2. Arthritis & Rheumatism, 65: 378–387. doi: 10.1002/art.37782
- Issue published online: 28 JAN 2013
- Article first published online: 28 JAN 2013
- Accepted manuscript online: 8 NOV 2012 01:52PM EST
- Manuscript Accepted: 25 OCT 2012
- Manuscript Received: 17 JUL 2012
- Arthritis Research UK. Grant Number: 18261
- Biotechnology and Biological Sciences Research Council. Grant Number: BBSRC grant BB/I020748/1
- JGWP Patterson Foundation
- Newcastle University Hospitals Special Trustees, UK
- NIHR Newcastle Biomedical Research Centre based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University
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.
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.
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.
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.