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

Aigner, T., Fundel K, Saas J, Gebhard PM, Haag J, Weiss T, Zien, A., Obermayr F, Zimmer, R., & Bartnik, E. (2006). Large-Scale Gene Expression Profiling Reveals Major Pathogenetic Pathways of Cartilage Degeneration in Osteoarthritis. Arthritis and Rheumatism, 54(11), 3533-3544. doi:10.1002/art.22174.

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Aigner, T, Autor
Fundel K, Saas J, Gebhard PM, Haag J, Weiss T, Zien, A1, Autor           
Obermayr F, Zimmer, R, Autor
Bartnik, E, Autor
Affiliations:
1Department Empirical Inference, Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_1497795              

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 Zusammenfassung: 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 gt;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.

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 Datum: 2006-10
 Publikationsstatus: Erschienen
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Titel: Arthritis and Rheumatism
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 54 (11) Artikelnummer: - Start- / Endseite: 3533 - 3544 Identifikator: -