[A new mechanism of action of chondroitin sulfates ACS4-ACS6 in osteoarthritic cartilage].
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.
Mathieu
Pierre
P
Service de rhumatologie du Pr Vignon, CH Lyon Sud, 165, chemin du Grand Revoyet, 69495 Pierre-Bénite. pierre-.mathieu.rhumato@wanadoo.fr
D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D002809:Chondroitin Sulfates / Q000494:pharmacology* / Q000627:therapeutic use; D003094:Collagen / Q000378:metabolism; D024043:Collagen Type II / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005353:Fibronectins / Q000096:biosynthesis; D005434:Flow Cytometry; D006706:Homeostasis; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D007375:Interleukin-1 / Q000502:physiology; D010003:Osteoarthritis / Q000188:drug therapy / Q000378:metabolism*; D020370:Osteoarthritis, Knee / Q000378:metabolism; D011817:Rabbits; D013997:Time Factors
D024043:Collagen Type II; D005353:Fibronectins; D007375:Interleukin-1; D007334:Insulin-Like Growth Factor I; D002809:Chondroitin Sulfates; D003094:Collagen