Extracellular matrix molecules of cartilage and their use as markers of cartilage alteration in joint disease

Journal/Book: Z Rheumatol 1998; 57: 174. 1998;

Abstract: Prof. Dr. D. Heinegård; Dept. of Cell and Molecular Biology Section for Connective Tissue Disease Lund University Lund Joint disease is characterized by early alterations in cartilage matrix constituents by far preceding alterations observed directly by arthroscopy as well as by MRI and x-ray imaging. To understand the early processes that lead to cartilage destruction it is important to understand the composition of cartilage at the molecular level and the organization and functional properties of the constituent macromolecules. Cartilage contains two major functional molecular organizations. One is the collagen fibrils forming a network resisting the forces exerted by the swelling pressure of the major other macromolecular constituent the large proteoglycans. Thus aggrecan contains a vast number of charged groups that are retained in the tissue being fixed there by the association to the protein in these molecules. These charge groups create an osmotic environment imbibing water. However the swelling pressure induced by this is resisted by the collagen fibrillar network. In this network a number of interactions between neighbouring fibrils mediated by fibril surface associated molecules are of key importance. It appears that early in arthrosis a significant alteration is a failure of the network probably caused by degradation of the cross-bridging molecules of the collagen network. Today little is known about such events and what are the agents involved. However tools are being developed to monitor these early processes by making use of the fact that fragmentation of the tissue constituent macromolecules creates fragments released into surrounding synovial fluid and eventually to the general circulation. The level of these fragments can be used to indicate the activity level of the process and the character of the fragment will indicate the stage and potentially mechanisms behind the tissue destruction. ... le

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