Anabolic and catabolic markers of proteoglycan metabolism in osteoarthritis

Abstract

Over the past 16 years our laboratories have focused on the development and use of immunological procedures to study cartilage structure, function and metabolism in health and disease (1). Most recently we have used monoclonal antibody technology to identify subtle changes that occur in the biochemistry of cartilage proteoglycans during the pathogenesis of osteoarthritis (2, 3). Changes in chondrocyte metabolism in OA produce compositional changes in the newly synthesized proteoglycans that occur in an attempt to remodel or repair the tissue in its response to its altered mechanical environment. These subtle changes in cartilage biochemistry can be detected by antibodies that recognize anabolic neoepitopes, (a new epitope that is generated in a biological molecule as a result of either changes in anabolic or catabolic processes in metabolism), in these newly synthesized proteoglycans. Similarly, increases in proteoglycan degradation (catabolism) also occur in the early pathogenesis of OA; this increased catabolism eventually leading to mechanical destruction of the tissue. Recently we developed monoclonal antibodies that specifically detect newly formed N- or C-terminal sequences (catabolic neoepitopes) on proteoglycan degradation products that result from this increased catabolism (4–6). Identification of these catabolic neoepitopes allows one to distinguish between the action(s) of putative proteolytic enzymes involved in normal proteoglycan turnover and specific degradation during the pathogenesis of osteoarthritis. In this review, we will describe work where we have developed and utilized monoclonal antibody technologies to identify both “anabolic” and “catabolic” markers of proteoglycan metabolism that are manifested during the pathogenesis of arthritis.