The etiology of OA is multi-factorial involving both mechanical and biochemical factors. OA progression is associated with increased cartilage degradation which leads to joint space narrowing (JSN), painful joint disruption, and loss of function. Osteoarthritis occurs due to change in dynamic equilibrium between the breakdown and repair of joint tissues is overwhelmed..
Traditionally, OA has been considered a disease of articular cartilage. Recently due to improvement in MRI imaging, there is an increased understanding of the other tissues in the pathophysiology of OA. OA involves the entire joint organ, including the subchondral bone, menisci, ligaments, muscle, capsule and synovium.
The pathology reflects the result of and response to joint failure, with loss and erosion of articular cartilage, subchondral bone alterations, meniscal degeneration, a synovial inflammatory response, and bone and cartilage growth (osteophytes).
Traditionally OA has been thought to be non-inflammatory disease. However, in the last decade, Dr.Abramson and his group have reported that OA cartilage produces inflammatory mediators such as nitric oxide, prostaglandin E2 and other pro inflammatory cytokines locally which leads to joint deterioration (Figure 1). Currently, large amounts of data provide support for a central role of IL-1 in the pathogenesis of OA including animal susceptibility models, models of IL-1-targeted therapy, genetic association studies, and elevated IL-1 gene expression in whole blood from patients with multi-joint OA.
The completion of the human genome sequencing project has represented a revolutionary advance in the field of human genetics. The simultaneous identification of large numbers of single nucleotide polymorphisms (SNPs), coupled with the development of rapid, high-throughput genotyping methods, has provided researchers with unprecedented tools for pharmacogenomic and proteomic biomarker research. In the post genomics era, the global methods of analysis RNA & DNA (genomics), protein (proteomics) and metabolites such as lipids (metabolimics) are defines as “omics” technologies. The functional genomics inclusive of all omics is a new way to address complex diseases such osteoarthritis and rheumatoid arthritis on a molecular level to better understand the pathophysiological process of the disease. Currently in our laboratories we are studying the global changes in biochemical pathways and structural genetics (DNA polymorphism) among the disease patients and healthy controls using various genomics and proteomics approaches to develop novel targets. Additionally, functional genomics is a new way to monitor the degradative events in the cartilage and to study biological and physical properties of cartilage extracellular matrix altered by disease or ageing processes in osteoarthritis on a molecular level to understand better the pathophysiological process of the disease and to develop novel targets for pharmacological intervention as current therapy focuses on pain relief and there is no FDA-approved therapy that arrests or reverses the joint deterioration in OA.