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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.

Original publication

DOI

10.1002/path.1190

Type

Journal article

Journal

J Pathol

Publication Date

10/2002

Volume

198

Pages

220 - 227

Keywords

Antibodies, Monoclonal, Cell Culture Techniques, Cell Differentiation, Glycoproteins, Humans, Interleukin-1, Leukocytes, Mononuclear, Macrophage Colony-Stimulating Factor, Osteoclasts, Osteoprotegerin, Receptors, Cytoplasmic and Nuclear, Receptors, Tumor Necrosis Factor, Recombinant Proteins, Tumor Necrosis Factor-alpha