SPECIALIZED CENTER OF RESEARCH IN OSTEOARTHRITIS

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This proposed Specialized Center of Research (SCOR) in osteoarthritis (OA) takes advantage of existing associations of researchers in the Indiana University Multipurpose Arthritis Center, who are already focused on problems relevant to OA. New inter-related projects by this highly interactive group of investigators are described. The proposal is developed from the perspective that OA does not represent failure merely of joint cartilage, but of an entire organ, the diarthrodial joint which is comprised of subchondral bone, synovium, ligaments and the neuromuscular apparatus, as well as cartilage. Five projects are proposed. One examines the potential of a specific non-collagenous cartilage matrix glycoprotein (CGMP) to serve as a noninvasive marker of OA and a means to monitor the course of the disease and response to treatment. It aims also to determine whether release of CGMP into serum and synovial fluid in OA is due to decreased cartilage matrix integrity or altered breakdown of CGMP. A second project examines the pericellular matrix (PCM), through which pass all materials entering and exiting the chondrocyte. Since proteoglycans and types IX and XI collagen in PCM may be degraded by increased chondrocyte-mediated protease activity in OA, studies of isolated chondrocytes, chondrones and organ cultures will compare synthesis, degradation and repair of PCM in OA and normal cartilage. A third project examines the importance of protective shielding against joint breakdown in OA. Two projects deal with the synovium: one assesses the importance of synovial inflammation in facilitating repair of cartilage in OA by examining effects of radiosynoviorthesis and low-dose corticosteroid therapy on cartilage changes in canine OA. The second is a clinical research project, which deals with the importance of synovitis as a cause of pain in OA tasks whether treatment with a nonsteroidal anti-inflammatory drug is more effective in providing symptomatic relief in OA than treatment only with an analgesic. The individual projects are supported by five core units: Biochemistry, Biostatistics, Histology/Photomicrography, Orthopedic Procedures and Administration.