Jorn Zwingmann, Bernhard Setzer, Markus Grobe Perdekamp, Wolfgang Schlickewei, Norbert P Sudkamp, Chingching Foocharoen and Ulrich A Walker
Background: The pathogenesis of osteoarthritis (OA) has been linked with the elaboration of increased amounts of nitrotyrosine in cartilage as a stable marker of tyrosine nitration by nitric oxide. Reactive oxygen species (ROS) are known to damage mitochondrial DNA (mtDNA); this process is associated with aging of non-cartilaginous tissues. This study aimed to link intraarticular nitrotyrosine content, with mtDNA lesions and OA severity in order to gain insights into the contribution of nitrotyrosine and mitochondria to cartilage aging and the development of OA.
Methods: Femoral heads were prospectively obtained from individuals undergoing hip arthroplasty or postmortem autopsy (22 male, 26 female, age range 16-93 years). OA severity was graded radiographically, and histologically by means of the Mankin score. Articular chondrocytes were isolated, and the ‘common’ mtDNA deletion quantified with a Polymerase Chain Reaction (PCR) technique. mtDNA copy numbers per chondrocyte were determined by quantitative PCR. Articular nitrotyrosine content in chondrocytes was quantified by ELISA. Multivariate associations between parameters were computed by linear regression analysis or Spearman rank correlations, as appropriate.
Results: Articular nitrotyrosine concentrations were independently correlated with both, the age of the subjects (r=0.39, p=0.01) and the presence of the common deletion (r=0.48, p=0.004), but not with the Mankin Score (p=0.84) or wild type mtDNA copy numbers. The severity of hip OA (Mankin score) however was only correlated with patient age, but not with articular nitrotyrosine, mtDNA deletions or wild type mtDNA copy numbers.
Conclusions: mtDNA lesions are correlated with articular nitrotyrosine content in hip cartilage, but a link of mitochondrial mutagenesis and NO-mediated ROS formation with the age of the subjects, or with OA severity cannot be demonstrated in this study.