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

2006

Article

ei


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.

Author(s): 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.
Journal: Arthritis and Rheumatism
Volume: 54
Number (issue): 11
Pages: 3533-3544
Year: 2006
Month: October
Day: 0

Department(s): Empirical Inference
Bibtex Type: Article (article)

Digital: 0
DOI: 10.1002/art.22174
Language: en
Organization: Max-Planck-Gesellschaft
School: Biologische Kybernetik

Links: Web

BibTex

@article{3852,
  title = {Large-Scale Gene Expression Profiling Reveals Major Pathogenetic Pathways of Cartilage Degeneration in Osteoarthritis},
  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.},
  journal = {Arthritis and Rheumatism},
  volume = {54},
  number = {11},
  pages = {3533-3544},
  organization = {Max-Planck-Gesellschaft},
  school = {Biologische Kybernetik},
  month = oct,
  year = {2006},
  month_numeric = {10}
}