gms | German Medical Science

Deutscher Kongress für Orthopädie und Unfallchirurgie
74. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie
96. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie
51. Tagung des Berufsverbandes der Fachärzte für Orthopädie und Unfallchirurgie

26. - 29.10.2010, Berlin

Somatically acquired and radical associated damage of mitochondrial DNA in osteoarthritis

Meeting Abstract

  • J. Zwingmann - Universitätsklinikum Freiburg, Department für Orthopädie und Traumatologie, Freiburg, Germany
  • B. Setzer - Universitätsklinikum Freiburg, Rheumatologie, Freiburg, Germany
  • M. Große Perdekamp - Universistätsklinikum Freiburg, Gerichtsmedizin, Freiburg, Germany
  • W. Schlickewei - St. Josefskrankenhaus Freiburg, Unfall- und Wiederherstellungschirurgie, Freiburg, Germany
  • N. P. Südkamp - Universitätsklinikum Freiburg, Department für Orthopädie und Traumatologie, Freiburg, Germany
  • U. Walker - Universitätsklinikum Freiburg, Rheumatologie, Freiburg, Germany

Deutscher Kongress für Orthopädie und Unfallchirurgie. 74. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 96. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie, 51. Tagung des Berufsverbandes der Fachärzte für Orthopädie. Berlin, 26.-29.10.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocIN22-750

DOI: 10.3205/10dkou133, URN: urn:nbn:de:0183-10dkou1332

Veröffentlicht: 21. Oktober 2010

© 2010 Zwingmann et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective: Idiopathic osteoarthritis (OA) is a degenerative joint disease with age-associated cartilage breakdown. The mitochondrial theory of aging suggests that chronic production of reactive oxygen species (ROS) within aging mitochondria is associated with loss of cellular function. ROS may in turn induce lesions within mitochondria and its genome (mitochondrial DNA, mtDNA), thereby closing a vicious circle. In chondrocytes however, detailed investigations about ROS- and age-mediated acquisition of mtDNA-damage have not been carried out.

Methods: Femoral heads were obtained from consecutive individuals undergoing hip arthoplasty and from autopsies. The degree of OA was determined with the radiological Kellgren and Lawrence and the histological Mankin score. Chondrocytes were isolated and nitrotyrosine content, a marker of ROS formation was determined by ELISA. Wild type and deleted mtDNA-copy numbers per chondrocyte were quantified with light-cycler based quantitative polymerase chain reactions.

Results and conclusions: Cartilage from 50 individuals (16–93 years) was analyzed. Age correlated with the Mankin score (p<0.001, r=0.58). Nitrotyrosine content within cartilage correlated with age (p=0.004, r=0.41) and the frequency of the 4977-bp “common” mtDNA deletion (p<0.001, r=0.49). Wild-type mtDNA copy numbers were unchanged in osteoarthritic compared to normal cartilage. In addition to the common mtDNA deletion, multiple further large-scale mtDNA rearrangements were detected in OA lesions. In multiple linear regression analysis Mankin and Kellgren and Lawrence score was predicted by both, nitrotyrosine content and age.

An increase of ROS in human cartilage, which plays a role in the development of OA, is highly significant correlated with an increase of alterations of mtDNA and age. The latter may have an impact on disease progression. Further studies are needed, to give us a better understanding of the ROS production in and around cartilage and their potential destructive effect on mtDNA and so to a possible damage to the resperatory chain, which is particualary in a hypoxix tissue almost without blood supply essentially.