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

2001; Elsevier BV; Volume: 31; Issue: 1 Linguagem: Inglês

10.1053/sarh.2000.24874

1532-866X

Jean-Pierre Balì, Henri Cousse, E Neuzil,

Protease and Inhibitor Mechanisms

Chondroitin sulfates (CS) are involved in articular metabolism and could be used as therapeutic agents in degenerative articular diseases.To review the published reports describing both the metabolism of glycosaminoglycans (GAG) and their involvement in osteoarticular pathophysiology.MEDLINE search for relevant articles and review of cited references.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 aggregates 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 cartilaginous 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 numerous matrix (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 proteoglycan production by chondrocytes; they also inhibit cartilage cytokine production 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.All these data suggest that CS play a role in articular and bone metabolism by controlling cartilaginous matrix integrity and bone mineralization.