A new mechanism of action of chondroitin sulfates ACS4-ACS6 in osteoarthritic cartilage
Mathieu, P.
Presse Medicale 31(29): 1383-1385
2002
ISSN/ISBN: 0755-4982 PMID: 12375394 Document Number: 544215
THE MECHANISMS OF ACTION ALREADY KNOWN: In vitro, chondroïtin sulfate ACS4-ACS6 have a dose-dependent inhibiting effect on the catabolism of proteoglycanes and collagen. They also stimulate the synthesis of extracellular matrix macromolecules. The existence of a chondrocyte cyto-protector effect and a potentially chondro-protective effect has also been demonstrated. ANOTHER MECHANISM OF ACTION: A new regulation route of chondrocyte metabolism has been proposed in which the Insulin Growth Factor (IGF-1) impedes the catabolic effects of another cytokine, Interleukin 1 (IL-1), by increasing its antagonistic receptor. This control appears essential in the maintenance extracellular matrix homeostasis. CARTILAGE WITH OSTEOARTHRITIS: Chondrocytes from OA cartilage have the capacity to produce more constituting macromolecules of the extracellular matrix. Conversely, these same cells have a greater catabolic capacity. The enhanced activity of IL-1 and the concomitant decrease in its antagonistic receptors leads to the reduction in macromolecule levels in the extracellular matrix, produced in the Cell-associated matrix of OA chondrocytes. ANTI-CATABOLIC EFFECT: It has been demonstrated that ACS4-ACS6 are capable of neutralizing the enhanced catabolic capacity of activated human OA chondrocytes.