Haem oxygenase-1 regulates catabolic and anabolic processes in osteoarthritic chondrocytes.
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-1beta (IL-1beta) 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-1beta in OA cartilage and chondrocytes. Up-regulation of HO-1 by cobalt protoporphyrin IX significantly reduced glycosaminoglycan degradation elicited by IL-1beta 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-1beta. Our data thus suggest that HO-1 may be a factor regulating the degradation and synthesis of extracellular matrix components in OA.
Guillén
Mi
M
Department of Pharmacology, Faculty of Pharmacy, University of Valencia, Spain.
Megías
J
J
Gomar
F
F
Alcaraz
Mj
M
D000368:Aged; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D024043:Collagen Type II / Q000378:metabolism; D005260:Female; D051547:Heme Oxygenase-1 / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000201:enzymology / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology
D024043:Collagen Type II; D053583:Interleukin-1beta; D011509:Proteoglycans; D011524:Protoporphyrins; C007095:cobaltiprotoporphyrin; D007334:Insulin-Like Growth Factor I; D051547:Heme Oxygenase-1; D020782:Matrix Metalloproteinases