Nuclear factor-κB activation by type II collagen peptide in articular chondrocytes: its inhibition by hyaluronan via the receptors
Tadashi Yasuda1
5 July 2012
20 November 2012
7 December 2012
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Objective This study aimed to examine nuclear factor-jB (NF-jB) activation by a synthetic peptide from type II collagen fragment (CB12-II) and its inhibition by hyaluronan (HA) via its receptors, CD44, and intercellular adhesion molecule-1 (ICAM-1) in chondrocytes.
Methods Osteoarthritic cartilage explants or chondrocytes in monolayer were cultured with CB12-II. Secreted levels of matrix metalloproteinase (MMP)-13 in conditioned media and NF-jB activation in chondrocytes were determined by immunoblotting and enzyme-linked immunosorbent assay (ELISA). Cultures were pretreated with HA to evaluate the inhibitory effect on CB12-II action, and the role of HA receptors in HA effect was investigated using antibodies to CD44 and ICAM-1.
Results CB12-II stimulated phosphorylation and nuclear translocation of NF-jB, leading to increased MMP-13 production. HA suppressed NF-jB activation and MMP-13 induction by CB12-II. The individual antibody to CD44 or ICAM-1 partially reversed HA effect on CB12-II action, and both antibodies in combination completely blocked the HA effect.
Conclusions This study clearly demonstrates that CB12-II activates NF-jB for MMP-13 induction and that HA inhibits CB12-II action through interaction with CD44 and ICAM-1 in chondrocytes. HA administration into osteoarthritic joints could suppress the catabolic action of matrix degradation products such as CB12-II as a potent NF-jB inhibitor.
Chondrocyte, Hyaluronan, NF-κB, Osteoarthritis, Type II collagen