title: Activation of p38 mitogen-activated protein kinase is inhibited by hyaluronan via intercellular adhesion molecule-1 in articular chondrocytes stimulated with type II collagen peptide.
abstract: This study examined the activation of p38 mitogen-activated protein kinase with matrix metalloproteinase-13 (MMP-13) production by a synthetic peptide derived from type II collagen (CB12-II) and its inhibition by high molecular weight hyaluronan (HA) in chondrocytes. When cartilage explants or isolated chondrocytes in monolayer were incubated with CB12-II, the peptide (50 µM, 72 h) activated p38 in association with enhanced MMP-13 production. Inhibition studies with SB203580 (0.1 - 1 µM) indicated the requirement of p38 for CB12-II-induced MMP-13 production. Pretreatment with 2700 kDa HA (1 mg/ml, 1 h) resulted in significant suppression of CB12-II-stimulated MMP-13 production in cartilage as well as in chondrocyte monolayer cultures. HA (1 mg/ml) suppressed p38 activation by CB12-II, leading to a decrease in MMP-13 production. The antibody (20 µg/ml) to intercellular adhesion molecule-1 (ICAM-1), which has been recognized as a receptor of HA on chondrocytes, reversed the HA effect on CB12-II action. Thus, the present study clearly demonstrated that high molecular weight HA suppressed CB12-II-activated p38 via ICAM-1 in articular chondrocytes. HA could down-regulate the catabolic action of type II collagen fragments in osteoarthritic joints through the mechanism demonstrated in this study.
authors.affiliation: Department of Sports Medicine, Faculty of Budo and Sport Studies, Tenri University, Japan. tadyasu@sta.tenri-u.ac.jp
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yasuda
mesh_terms: D002358:Cartilage, Articular / Q000166:cytology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D024043:Collagen Type II / Q000494:pharmacology*; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D055675:Viscosupplements / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D024043:Collagen Type II; D010455:Peptides; D055675:Viscosupplements; D018799:Intercellular Adhesion Molecule-1; D006820:Hyaluronic Acid; D048051:p38 Mitogen-Activated Protein Kinases; D053509:Matrix Metalloproteinase 13