Identification and expression of novel genes in osteoarthritis
© BioMed Central Ltd 2001
Received: 6 April 2001
Published: 25 April 2001
Osteoarthritis (OA), the most common form of joint disease, represents a clinical classification of pathological conditions involving progressive degradation of articular cartilage and remodeling of subchondral bone. Genes whose products are involved in chondrogenesis and osteogenesis starting from the common progenitor cells, genes determining the terminal differentiation of chondrocytes and genes whose products trigger breakdown of the cartilaginous matrix are obvious candidates for therapeutic intervention. In this study we used human articular cartilage primary cells to conduct a series of gene expression profiling experiments. The cells were subjected to various treatments, which mimic OA initiation and development: IL-1β-FAD (FGF-2+Dexamethasone+Ascorbic acid) and mechanical stress. The gene expression profiles corresponding to various applied treatments were studied by microarray hybridization and analyzed by QBI's proprietary bioinformatics tools. The obtained gene expression patterns indicates that the chosen in vitro cell system accurately reflects the processes that occur in OA joints in vivo since many genes known to be markers of OA were identified by us as displaying the expected type of behavior. After performing the full analysis of hybridization results, a list of 254 genes was obtained. Among them are 210 known genes and 44 novel ones. Out of them 80 genes were further analyzed by in situ hybridization on sections obtained from OA patients and control group and by RT-PCR. 15 genes have shown promising results. Among them, genes whose expression was upregulated in chondrocytes located close to the eroded surface of the OA articular cartilage, in osteoprogenitor cells and in endothelial cells. Further studies are being conducted to analyze the role of these genes in OA.