title: Nuclear factor-κB activation by type II collagen peptide in articular chondrocytes: its inhibition by hyaluronan via the receptors.
abstract: OBJECTIVE
  This study aimed to examine nuclear factor-κB (NF-κB) 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-κB 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-κB, leading to increased MMP-13 production. HA suppressed NF-κB 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-κB 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-κB inhibitor.
authors.affiliation: Department of Sports Medicine, Faculty of Budo and Sports Studies, Tenri University, 80 Tainosho-cho, Tenri, Nara, 632-0071, Japan, tadyasu@sta.tenri-u.ac.jp.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yasuda
mesh_terms: D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D024043:Collagen Type II / Q000494:pharmacology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D020370:Osteoarthritis, Knee / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D010766:Phosphorylation
chemical_list: D024043:Collagen Type II; D018960:Hyaluronan Receptors; D016328:NF-kappa B; D010446:Peptide Fragments; D006820:Hyaluronic Acid; D053509:Matrix Metalloproteinase 13