Gene Mining and Functional Genomics in Human Osteoarthritis

Human osteoarthritis (OA) is a complex multi-factorial disease that primarily targets the cartilage. The cartilage is a specialized tissue where the chondrocytes maintain matrix homeostasis. The paradigm for the post genomic era of molecular medicine is to identify the function of defective genes associated with specific diseases. Although the process of identification and validation of target genes is feasible with the available tools and technologies, establishing the link between defected gene products and the disease is still a challenging task. New tools in genomic analysis not only allow us to profile gene expression in normal and diseased tissues, but also facilitate the development of unbiased hypothesis at the molecular level. Several defective heritable genes encoding the matrix components (such as Col2a1 and Col9a1 that code for type II and IX collagen respectively) have been linked to the development of OA in human and animal models. Several families of genes expressed differentially in normal and osteoarthritis-affected cartilage have been identified. These include matrix metalloproteinases (MMPs), matrix proteins, integrins, transcription factors, cytokines, cytokine receptors, growth factors and homeostatic genes. A non-conventional functional genomic approach is required to study the complexity of chondrocyte and matrix interactions that affect the above mentioned targets.