Large-Scale Gene Expression Profiling Reveals Major Pathogenetic Pathways of Cartilage Degeneration in Osteoarthritis

@article{3852,
  title = {Large-Scale Gene Expression Profiling Reveals Major Pathogenetic Pathways of Cartilage Degeneration in Osteoarthritis},
  journal = {Arthritis and Rheumatism},
  abstract = {Objective. Despite many research efforts in recent
  decades, the major pathogenetic mechanisms of osteo-
  arthritis (OA), including gene alterations occurring
  during OA cartilage degeneration, are poorly under-
  stood, and there is no disease-modifying treatment
  approach. The present study was therefore initiated in
  order to identify differentially expressed disease-related
  genes and potential therapeutic targets.
  Methods. This investigation consisted of a large
  gene expression profiling study performed based on 78
  normal and disease samples, using a custom-made
  complementar y DNA array covering >4,000 genes.
  Results. Many differentially expressed genes were
  identified, including the expected up-regulation of ana-
  bolic and catabolic matrix genes. In particular, the
  down-regulation of important oxidative defense genes,
  i.e., the genes for superoxide dismutases 2 and 3 and
  glutathione peroxidase 3, was prominent. This indicates
  that continuous oxidative stress to the cells and the
  matrix is one major underlying pathogenetic mecha-
  nism in OA. Also, genes that are involved in the
  phenot ypic stabilit y of cells, a feature that is greatly
  reduced in OA cartilage, appeared to be suppressed.
  Conclusion. Our findings provide a reference data set on gene alterations in OA cartilage and, importantly,
  indicate major mechanisms underlying central cell bio-
  logic alterations that occur during the OA disease
  process. These results identify molecular targets that
  can be further investigated in the search for therapeutic
  interventions.},
  volume = {54},
  number = {11},
  pages = {3533-3544},
  organization = {Max-Planck-Gesellschaft},
  school = {Biologische Kybernetik},
  month = oct,
  year = {2006},
  author = {Aigner, T. and Fundel, K. and Saas, J. and Gebhard, PM. and Haag, J. and Weiss, T. and Zien, A. and Obermayr, F. and Zimmer, R. and Bartnik, E.},
  doi = {10.1002/art.22174},
  month_numeric = {10}
}