IL (interleukin)-1β plays an important role in cartilage extracellular matrix degradation and bone resorption in OA (osteoarthritis) through the induction of degradative enzymes and pro-inflammatory mediators. In the present study, we have determined the consequences of HO-1 (haem oxygenase-1) induction on markers of inflammation and senescence in the functional unit cartilage–subchondral bone stimulated with IL-1β. Cartilage–subchondral bone specimens were obtained from the knees of osteoarthritic patients. Treatment with the HO-1 inducer CoPP (cobalt protoporphyrin IX) counteracted the stimulatory effects of IL-1β on IL-6, nitrite, PGE2 (prostaglandin E2), TGF (transforming growth factor) β2, TGFβ3 and osteocalcin. Immunohistochemical analyses indicated that CoPP treatment of explants down-regulated iNOS (inducible nitric oxide synthase), COX-2 (cyclooxygenase-2) and mPGES-1 (microsomal prostaglandin E synthase-1) induced by IL-1β. In contrast, the expression of HMGB1 (high-mobility group box 1) was not significantly modified. In addition, CoPP decreased the expression of iNOS and mPGES-1 in cells isolated from the explants and stimulated with IL-1β, which was counteracted by an siRNA (small interfering RNA) specific for human HO-1. In isolated primary chondrocytes, we determined senescence-associated β-galactosidase activity and the expression of senescence markers by real-time PCR. We have found that HO-1 induction could regulate senescence markers in the presence of IL-1β and significantly affected telomerase expression, as well as β-galactosidase activity and hTERT (human telomerase reverse transcriptase) and p21 expression in chondrocytes. The findings of the present study support the view that HO-1 induction results in the down-regulation of inflammatory and senescence responses in OA articular tissues.
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November 08 2011
Haem oxygenase-1 counteracts the effects of interleukin-1β on inflammatory and senescence markers in cartilage–subchondral bone explants from osteoarthritic patients
Victoria Clérigues;
Victoria Clérigues
*Department of Pharmacology, University of Valencia, and IDM, Av. Vicent A. Estellés s/n, 46100 Burjasot, Valencia, Spain
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Maria Isabel Guillén;
*Department of Pharmacology, University of Valencia, and IDM, Av. Vicent A. Estellés s/n, 46100 Burjasot, Valencia, Spain
†Department of Chemistry, Biochemistry and Molecular Biology, Cardenal Herrera-CEU University, Ed. Seminario, 46113 Moncada, Valencia, Spain
Correspondence: Professor Maria José Alcaraz (email [email protected]).
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Francisco Gomar;
Francisco Gomar
‡Department of Surgery, Faculty of Medicine, University of Valencia, Av. Blasco Ibañez 15, 4610 Valencia, Spain.
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Maria José Alcaraz
Maria José Alcaraz
*Department of Pharmacology, University of Valencia, and IDM, Av. Vicent A. Estellés s/n, 46100 Burjasot, Valencia, Spain
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Publisher: Portland Press Ltd
Received:
October 25 2010
Revision Received:
September 08 2011
Accepted:
September 28 2011
Accepted Manuscript online:
September 28 2011
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2012 Biochemical Society
2012
Clin Sci (Lond) (2012) 122 (5): 239–251.
Article history
Received:
October 25 2010
Revision Received:
September 08 2011
Accepted:
September 28 2011
Accepted Manuscript online:
September 28 2011
Citation
Victoria Clérigues, Maria Isabel Guillén, Francisco Gomar, Maria José Alcaraz; Haem oxygenase-1 counteracts the effects of interleukin-1β on inflammatory and senescence markers in cartilage–subchondral bone explants from osteoarthritic patients. Clin Sci (Lond) 1 March 2012; 122 (5): 239–251. doi: https://doi.org/10.1042/CS20100519
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