Large-scale gene expression profiling reveals major pathogenetic pathways of cartilage degeneration in osteoarthritis. Export

@article{aigner_06_largescale, abstract = {OBJECTIVE: Despite many research efforts in recent decades, the major pathogenetic mechanisms of osteoarthritis (OA), including gene alterations occurring during OA cartilage degeneration, are poorly understood, 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 complementary DNA array covering >4,000 genes. RESULTS: Many differentially expressed genes were identified, including the expected up-regulation of anabolic 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 mechanism in OA. Also, genes that are involved in the phenotypic stability 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 biologic 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 = {Aigner, T. and Fundel, K. and Saas, J. and Gebhard, P. M. and Haag, J. and Weiss, T. and Zien, A. and Obermayr, F. and Zimmer, R. and Bartnik, E.}, citeulike-article-id = {3409620}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/art.22174}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17075858}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17075858}, citeulike-linkout-3 = {http://dx.doi.org/http://dx.doi.org/10.1002/art.22174}, citeulike-linkout-4 = {http://dx.doi.org/10.1002/art.22174}, comment = {Cited by davis\_06\_reliable}, doi = {10.1002/art.22174}, issn = {0004-3591}, journal = {Arthritis and rheumatism}, keywords = {microarray, proj\_stabperf}, month = {November}, number = {11}, pages = {3533--3544}, posted-at = {2008-10-15 15:28:53}, priority = {1}, title = {Large-scale gene expression profiling reveals major pathogenetic pathways of cartilage degeneration in osteoarthritis.}, url = {http://dx.doi.org/10.1002/art.22174}, volume = {54}, year = {2006} }

TY - JOUR ID - aigner_06_largescale L3 - citeulike-article-id:3409620 N2 - OBJECTIVE: Despite many research efforts in recent decades, the major pathogenetic mechanisms of osteoarthritis (OA), including gene alterations occurring during OA cartilage degeneration, are poorly understood, 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 complementary DNA array covering >4,000 genes. RESULTS: Many differentially expressed genes were identified, including the expected up-regulation of anabolic 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 mechanism in OA. Also, genes that are involved in the phenotypic stability 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 biologic alterations that occur during the OA disease process. These results identify molecular targets that can be further investigated in the search for therapeutic interventions. IS - 11 JF - Arthritis and rheumatism SN - 0004-3591 EP - 3544 TI - Large-scale gene expression profiling reveals major pathogenetic pathways of cartilage degeneration in osteoarthritis. VL - 54 SP - 3533 KW - microarray KW - proj_stabperf N1 - Cited by davis_06_reliable AU - Aigner, T AU - Fundel, K AU - Saas, J AU - Gebhard, PM AU - Haag, J AU - Weiss, T AU - Zien, A AU - Obermayr, F AU - Zimmer, R AU - Bartnik, E PY - 2006/November// UR - http://dx.doi.org/10.1002/art.22174 ER -