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

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. © the japanese pharmacological society.