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Haem oxygenase‐1 regulates catabolic and anabolic processes in osteoarthritic chondrocytes
Author(s) -
Guillén MI,
Megías J,
Gomar F,
Alcaraz MJ
Publication year - 2008
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2313
Subject(s) - cartilage , anabolism , catabolism , chemistry , extracellular matrix , matrix metalloproteinase , glycosaminoglycan , aggrecan , osteoarthritis , extracellular , interleukin , proinflammatory cytokine , endocrinology , microbiology and biotechnology , medicine , biochemistry , inflammation , cytokine , biology , pathology , enzyme , anatomy , alternative medicine , articular cartilage
Pro‐inflammatory cytokines, matrix metalloproteinases (MMPs) and other catabolic factors participate in the pathogenesis of cartilage damage in osteoarthritis (OA). Pro‐inflammatory cytokines such as interleukin‐1β (IL‐1β) mediate cartilage degradation and might be involved in the progression of OA. Previously, we found that haem oxygenase‐1 (HO‐1) is down‐regulated by pro‐inflammatory cytokines and up‐regulated by IL‐10 in OA chondrocytes. The aim of this study was to determine whether HO‐1 can modify the catabolic effects of IL‐1β in OA cartilage and chondrocytes. Up‐regulation of HO‐1 by cobalt protoporphyrin IX significantly reduced glycosaminoglycan degradation elicited by IL‐1β in OA cartilage explants but increased glycosaminoglycan synthesis and the expression of collagen II in OA chondrocytes in primary culture, as determined by radiometric procedures, immunoblotting and immunocytochemistry. HO‐1 decreased the activation of extracellular signal‐regulated kinase 1/2. This was accompanied by a significant inhibition in MMP activity and expression of collagenases MMP‐1 and MMP‐13 at the protein and mRNA levels. In addition, HO‐1 induction caused a significant increase in the production of insulin‐like growth factor‐1 and a reduction in the levels of insulin‐like growth factor binding protein‐3. We have shown in primary culture of chondrocytes and articular explants from OA patients that HO‐1 counteracts the catabolic and anti‐anabolic effects of IL‐1β. Our data thus suggest that HO‐1 may be a factor regulating the degradation and synthesis of extracellular matrix components in OA. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.