Biochemical Basis of the Pharmacologic Action of Chondroitin Sulfates on the Osteoarticular System

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 patho-physiology. Methods: MEDLINE search for relevant articles and review of cited references. Results: 1) CS are formed of disaccharide units; sulfated galactosamine residues 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-linkages leads to aggre-gates of monomers with high molecular weights. The proteoglycan aggregate exhibits viscoelastic and hydration properties and an ability to interact with the surrounding tissue through electric charges leading to protection of the cartilag-inous tissues. 2) CS are synthesized both in chondrocytes and in bone cells by the action of specific glycosyl-transferases; their catabolism occurs in the matrix and involves numerousmatrix (metalloproteinases) and lysosomal enzymes. 3) CS are inhibitors of extracellular proteases involved in the metabolism of connective tissues. In addition to their anti-inflammatory effects, CS in vitro stimulate pro-teoglycan production by chondrocytes; they also inhibit cartilage cytokine pro-duction and induce apoptosis of articular chondrocytes. CS increase the intrinsic viscosity of the synovial liquid. 4) In vivo in experimental arthritis, the number 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 bone me-tabolism by controlling cartilaginous matrix integrity and bone mineralization