Growth plate cartilage as developmental model in osteoarthritis research - Potentials and limitations

Gene expression analysis including large scale gene expression profiling has become a very basic tool for investigating the pathogenesis of degenerative joint diseases as well as for the search of new drug targets. However, gene expression analysis so far revealed very complex expression patterns rather than a clear picture of molecular changes occurring during the initiation and progression of the disease. To elucidate the molecular changes in osteoarthritis the analysis of the fetal growth plate as a developmental model for phenotypic changes in chondrocytes occurring in osteoarthritis can help in three ways: it allows to interpret gene expression patterns in the context of disease-relevant processes also occurring in developing cartilage (e.g. cell differentiation, proliferation, matrix synthesis, catabolism and calcification), it offers the chance to investigate gene function in these functional contexts by knocking out or overexpressing genes in animals, and it provides a suitable model for testing the effect of therapeutic compounds on these processes within the growing cartilage.