Recombinant human interferon-γ inhibits formation of human osteoclast-like cells

N. Takahashi, G. R. Mundy, G. D. Roodman

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Abstract

Interferon-γ (IFN-γ) inhibits osteoclastic bone resorption in vitro, but the mechanism responsible for this inhibition is unknown. We have used a long-term human marrow culture system that forms multinucleated cells (MNC) with osteoclast characteristics to test the effect of recombinant human IFN-γ on MNC formation. The addition of 1,25-dihydroxyvitamin D3 (1,25D3) at 10-8 M to these cultures significantly increased both MNC formation and the number of nuclei per MNC. IFN-γ at 100 U/ml strongly inhibited both of these effects of 1,25D3 in this system. IFN-γ significantly inhibited MNC formation at very low concentrations (4 U/ml), with 10 U/ml inhibiting 1,25D3-stimulated MNC formation by 50%. In contrast, 100 U/ml of IFN-γ were required to inhibit the growth of granulocyte-macrophage colony-forming cells, the probable progenitor for MNC, by 50%. Treatment of cultures with IFN-γ for only the first or last week of culture significantly inhibited MNC formation stimulated by 1,25D3. Autoradiographic studies with [3H]thymidine showed that IFN-γ did not inhibited proliferation of precursors for MNC. Additionally, IFN-γ inhibited MNC formation stimulated by parathyroid hormone or interleukin-1. These results suggest that IFN-γ inhibits MNC formation, and that IFN-γ inhibits bone resorption in part by inhibiting osteoclast formation.

Original languageEnglish (US)
Pages (from-to)3544-3549
Number of pages6
JournalJournal of Immunology
Volume137
Issue number11
StatePublished - Dec 1 1986

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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