Article (Scientific journals)
Enhanced osteoclast development in collagen-induced arthritis in interferon-gamma receptor knock-out mice as related to increased splenic CD11b(+) myelopoiesis
De Klerck, Bert; Carpentier, Isabelle; Lories, Rick J et al.
2004In Arthritis Research and Therapy, 6 (3), p. 220-R231
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Keywords :
osteoclast differentiation factor; osteoprotegerin ligand; receptor activator of NF-kappa B ligand; tumour necrosis factor receptor-associated factor
Abstract :
[en] Collagen-induced arthritis (CIA) in mice is accompanied by splenomegaly due to the selective expansion of immature CD11b(+) myeloblasts. Both disease manifestations are more pronounced in interferon-gamma receptor knock-out (IFN-gammaR KO) mice. We have taken advantage of this difference to test the hypothesis that the expanding CD11b(+) splenic cell population constitutes a source from which osteoclast precursors are recruited to the joint synovia. We found larger numbers of osteoclasts and more severe bone destruction in joints of IFN-gammaR KO mice than in joints of wild-type mice. Osteoclast-like multinucleated cells appeared in splenocyte cultures established in the presence of macrophage colony-stimulating factor (M-CSF) and stimulated with the osteoclast-differentiating factor receptor activator of NF-kappaB ligand (RANKL) or with tumour necrosis factor-alpha (TNF-alpha). Significantly larger numbers of such cells could be generated from splenocytes of IFN-gammaR KO mice than from those of wildtype mice. This was not accompanied, as might have been expected, by increased concentrations of the intracellular adaptor protein TRAF6, known to be involved in signalling of RANKL- and TNF-alpha-induced osteoclast formation. Splenocyte cultures of IFN-gammaR KO mice also produced more TNF-alpha and more RANKL than those of wild-type mice. Finally, splenocytes isolated from immunised IFN-gammaR KO mice contained comparatively low levels of pro-interleukin-1beta (pro-IL-1beta) and pro-caspase-1, indicating more extensive conversion of pro-IL-1beta into secreted active IL-1beta. These observations provide evidence that all conditions are fulfilled for the expanding CD11b(+) splenocytes to act as a source of osteoclasts and to be indirectly responsible for bone destruction in CIA. They also provide a plausible explanation for the higher susceptibility of IFN-gammaR KO mice to CIA.
Disciplines :
Rheumatology
Author, co-author :
De Klerck, Bert;  Katholieke Universiteit Leuven - KUL > Riga Institute
Carpentier, Isabelle;  Ghent University > DMBR
Lories, Rick J;  Katholieke Universiteit Leuven - KUL > Skeletal Development and joint disorders
Habraken, Yvette ;  Université de Liège - ULiège > Virologie - Immunologie
Piette, Jacques ;  Université de Liège - ULiège > Département des sciences de la vie > Virologie - Immunologie
Carmeliet, Geert;  Katholieke Universiteit Leuven - KUL > Experimental medecine and Endocrinology
Beyaert, Rudi;  Ghent University > DMBR
Billiau, Alfons;  Katholieke Universiteit Leuven - KUL > Riga Institute
Matthys, Patrick;  Katholieke Universiteit Leuven - KUL > Riga Institute
Language :
English
Title :
Enhanced osteoclast development in collagen-induced arthritis in interferon-gamma receptor knock-out mice as related to increased splenic CD11b(+) myelopoiesis
Publication date :
2004
Journal title :
Arthritis Research and Therapy
ISSN :
1478-6354
eISSN :
1478-6362
Publisher :
Biomed Central Ltd, London, United Kingdom
Volume :
6
Issue :
3
Pages :
R220-R231
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
Interuniversity Attraction Pole Program (IUAP)
Concerted Research Actions (GOA)
Funders :
Gouvernement Fédéral Belge [BE]
FWO - Fonds Wetenschappelijk Onderzoek Vlaanderen [BE]
Flemish Government [BE]
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