The purpose of this research proposal is to continue the study of normal and pathological articular and epiphyseal cartilage with special attention to the metabolims of the tissue in health and a variety of disease states, especially human osteoarthritis. The studies to be performed include a continued study of DNA replicative activity in normal and pathological cartilages with special emphasis on the use of flow cytometry; a continued definition of the products and rates of synthesis of normal and pathologic cartilages utilizing a variety of biochemical and metabolic techniques including the cell-free systems; a continued study of a variety of normal and pathological control mechanisms of the metabolic (both anabolic and catabolic) activities of normal and abnormal cartilages; a search for intracellular and cell membrane markers of disease states in normal and pathologic cartilages, chiefly by use of the flow cytometer; and continued attempts at isolation, identification, purification and determination of optimal conditions, substrate, cofactors and inhibitors for degradative enzymes in normal and diseased articular and epiphyseal cartilages.