We have recently developed an ELISA which makes use of a specific monoclonal antibody to determine levels of keratan sulfate (KS) in blood. We have already shown that blood levels of KS, a molecule found almost exclusively in cartilage proteoglycans, are a direct measure of the tissue. We have obtained preliminary evidence that KS levels are higher in patients with osteoarthritis than in age-matched controls. The purposes of the present studies are to determine if the elevations in KS levels reflect an increase cartilage proteoglycan degradation which is restricted to """"""""osteoarthritic"""""""" joints or a systemic elevated state of cartilage proteoglycans in all cartilages. First, we will compare serum levels of KS in patients with well defined forms of osteoarthritis and in age-matched controls. Levels of KS will be correlated to the clinical picture. Second, selected patients will be tested at various times before as well as after removal of destroyed cartilage at arthroplasty. This will help determine of removal of degenerating cartilages results in a decrease of KS blood levels to more normal values. Third, we propose to use and animal model to examine the sequence of events which begins with the loss of KS-bearing molecules from cartilage and ends with the elimination of KS chains from the circulation. Finally, we propose to determine if there are any differences in the chemical composition of the KS chains found in the circulation of patients with osteoarthritis and age-matched controls. We will characterize 15 antibodies which appear to be specific for KS to determine if one or more of these antibodies preferentially detects an epitope found in the disease state in order to seek an even better tool to monitor abnormal catabolism of cartilage proteoglycans. These studies will help define more precisely the usefulness of measurements of serum KS levels in osteoarthritis.
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