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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 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.
