Biochemical basis of the pharmacologic action of chondroitin sulfates on the osteoarticular system

Background. Chondroitin sulfates (CS) are involved in articular metabolism and could be used as therapeutic agents in degenerative articular diseases. Objectives: To review the published reports describing both the metabolism of glycosaminoglycans (GAG) and their involvement in osteoarticular pathoph ysiology. Methods. MEDLINE search for relevant articles and review of cited reference s. Results. 1) CS are formed of disaccharide units; sulfated galactosamine res idues in position 4 or 6 are found in various ratios, depending on the age and the type of tissue. Binding to the core protein through N- and O-linkag es leads to aggregates of monomers with high molecular weights. The proteog lycan aggregate exhibits viscoelastic and hydration properties and an abili ty to interact with the surrounding tissue through electric charges leading to protection of the cartilaginous tissues. 2) CS are synthesized both in chondrocytes and in bone cells by the action of specific glycosyl-transfera ses; their catabolism occurs in the matrix and involves numerous matrix (me talloproteinases) and lysosomal enzymes. 3) CS are inhibitors of extracellu lar proteases involved in the metabolism of connective tissues. In addition to their anti-inflammatory effects, CS in vitro stimulate proteoglycan pro duction by chondrocytes; they also inhibit cartilage cytokine production an d induce apoptosis of articular chondrocytes. CS increase the intrinsic vis cosity of the synovial liquid. 4) In vivo in experimental arthritis, the nu mber and severity of articular symptoms decreases after CS administration. In bones, CS accelerate the mineralization process and bone repair. Conclusions. All these data suggest that CS play a role in articular and bo ne metabolism by controlling cartilaginous matrix integrity and bone minera lization. Copyright (C) 2001 by W.B. Saunders Company.