Genomics of osteoarthritis

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Abstract
This review addresses the progress in three major fields of "genomics of osteoarthritis" over the past year: genetic alterations thought to be important for the initiation and progression of osteoarthritis, differential gene expression analysis, and functional genomics of osteoarthritis. Distinct genetic risk factors may predispose different joint sites to osteoarthritis, and although clear loci for susceptibility genes for common osteoarthritis have yet to emerge from the epidemiological studies, new approaches are narrowing down known loci. The search for specific genes using cDNA array technology has further demonstrated its potential in arthritis research as a powerful tool that could further provide biological insights into disease mechanisms, osteoarthritis polymorphic subtypes, the molecular validation of animal models, and the monitoring of drug activity on gene expression levels. Gene expression analysis has further characterized the striking shift in the gene expression pattern during "dedifferentiation" of chondrocytes in vitro as well as added depth to the phenotype of differentiated versus undifferentiated mesenchymal stem cells. Several new molecules potentially relevant to the disease process were identified, among them beta2-microglobulin (B2M), clusterin, and chitinase-like molecule 2. Functional genomic approaches will in the future allow to complement traditional biochemistry and molecular biology. Although there are limitations to cDNA array technology, "molecular portraits" of osteoarthritic chondrocytes in vivo and in vitro can be produced to analyze whole or large biologic systems rather than just single aspects of it. This will stimulate the testing of new markers, which are needed for the diagnosis and monitoring of osteoarthritis.

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