In mature articular cartilages, dermatan sulfate proteoglycans (DS-PGs) are located in high concentration in the superficial tangential zone and pericellular matrix of chondrocytes. Recent studies indicate that these are the areas where the earliest pathologic changes are seen in the articular cartilage degeneration which occurs during the development of human osteoarthritis. Degradation and loss of DS-PGs from the superficial tangential zone and pericellular matrix is almost certainly an important event which goes hand-in-hand with collagen fibril disruption during the development of these pathologic changes. However, appropriate studies have not yet been carried out to show that this is the case. One objective of the proposed studies is to determine whether degradation and loss of DS-PGs in the superficial tangential zone and pericellular matrix is an early initial event which precedes and leads to the development of overt fibrillation in articular cartilage degeneration. DS-PGs have important biochemical properties that affect the formation organization, stability and biologic properties of connective tissue extra-cellular matrices. Four types of DS-PGs have been isolated from articular cartilage and skin, which differ in the primary structures of their core proteins, the numbers of glycosaminoglycans (GAG) chains, and the IdoA-GalNAc(S04) content and structure of their GAG chains. These DS-PGs will be used to examine the relationship between the structure of a particular DS-PG and its biochemical and biologic properties. A major objective of the proposed studies is to determine the effect of structural differences in the DS-PGs on their biochemical and biological properties, i.e., their self-association into oligomers, their stoichiometry and affinity of binding to collagen fibrils, and their effects on collagen fibril formation and stability. The studies should provide a better understanding of the properties of the DS-PGs, and help explain how degeneration and loss of DS-PGs from the superficial regions of articular cartilage in the early stages of articular cartilage degeneration contributes to the development of osteoarthritis.
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