Proinflammatory cytokine (TNFα/IL‐1α) induction of human osteoclast formation

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Abstract
TNFα and IL-1α 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 TNFα (± IL-1α) is also capable of inducing human osteoclastogenesis. The CD14+ monocyte fraction of human peripheral mononuclear cells was cultured with TNFα ± IL-1α in the presence of M-CSF. TNFα induced the formation of multinucleated cells (MNCs) which were positive for TRAP, VNR and cathepsin K and showed evidence of resorption pit formation. IL-1α stimulated TNFα-induced lacunar resorption two- to four-fold. Osteoprotegerin, the decoy receptor for RANKL, did not inhibit this process. Anti-human IL-1α neutralizing antibodies significantly inhibited resorption without inhibiting the formation of TRAP+/VNR+ MNCs. These results suggest that, in the presence of M-CSF, TNFα is sufficient for inducing human osteoclast differentiation from circulating precursors by a process which is distinct from the RANK/RANKL signalling pathway. Copyright © 2002 John Wiley & Sons, Ltd.

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