title: Proinflammatory cytokine (TNFalpha/IL-1alpha) induction of human osteoclast formation.
abstract: TNFalpha and IL-1alpha are potent stimulators of bone resorption in vivo and in vitro. Recently, it has been demonstrated that these two cytokines directly induce osteoclastogenesis in mouse marrow cultures. This study determined whether TNFalpha (+/- IL-1alpha) is also capable of inducing human osteoclastogenesis. The CD14(+) monocyte fraction of human peripheral mononuclear cells was cultured with TNFalpha +/- IL-1alpha in the presence of M-CSF. TNFalpha induced the formation of multinucleated cells (MNCs) which were positive for TRAP, VNR and cathepsin K and showed evidence of resorption pit formation. IL-1alpha stimulated TNFalpha-induced lacunar resorption two- to four-fold. Osteoprotegerin, the decoy receptor for RANKL, did not inhibit this process. Anti-human IL-1alpha neutralizing antibodies significantly inhibited resorption without inhibiting the formation of TRAP(+)/VNR(+) MNCs. These results suggest that, in the presence of M-CSF, TNFalpha is sufficient for inducing human osteoclast differentiation from circulating precursors by a process which is distinct from the RANK/RANKL signalling pathway.
authors.affiliation: Department of Pathology, Nuffield Orthopaedic Centre, Windmill Road, Headington, University of Oxford, Oxford OX3 7LD, UK.
authors.forename: Osami
authors.initials: O
authors.lastname: Kudo
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Fujikawa
authors.forename: Ichiro
authors.initials: I
authors.lastname: Itonaga
authors.forename: Afsie
authors.initials: A
authors.lastname: Sabokbar
authors.forename: Takehiko
authors.initials: T
authors.lastname: Torisu
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Athanasou
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D006023:Glycoproteins / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D007375:Interleukin-1; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; C506030:TNFRSF11B protein, human; C506031:Tnfrsf11b protein, mouse; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor