Interferons-α and -γ inhibit interleukin-1β-stimulated osteoclast-like cell formation in long-term human marrow cultures

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Abstract

Immune cell products can have major effects on bone remodelling. Cytokines, such as interleukin-1 (IL-1), are potent stimulators of bone resorption, whereas interferon-γ (IFN-γ) inhibits bone resorption stimulated by these factors. Bone resorption is a result of either increased numbers of osteoclasts, increased activity of individual osteoclasts, or both. Recently, we have shown that human recombinant IFN-γ is a potent inhibitor of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-induced formation of multinucleated cells (MNC) that express the osteoclast phenotype. However, it is unknown if other IFNs share this capacity to inhibit MNC formation. Therefore, we tested the effects of natural IFNs-α and -γ and Escherichia coli-derived recombinant human IFN-γ on MNC formation and on granulocyte-macrophage (CFU-GM) colony formation (an early osteoclast precursor) in human marrow cultures treated with IL-1β or CSF-GM, respectively, to determine their effects on human osteoclast formation. Each type of IFN inhibited CFU-GM colony formation similarly in a dose-dependent fashion, with 50% inhibition seen at 64-250 U/ml. Natural or recombinant IFN-γ inhibited IL-1β-stimulated MNC formation in a dose-dependent manner with an ID50 of 1-16 U/ml. IFN-α was more potent that IFN-γ, with an ID50 of less than 1 U/ml. Furthermore, both IFN-α and -γ inhibited fusion of precursors of these multinucleated cells. These data demonstrate that IFNs-α and -γ inhibit MNC formation by inhibiting the growth of precursors for these cells as well as their subsequent fusion.

Original languageEnglish (US)
Pages (from-to)541-547
Number of pages7
JournalJournal of Interferon Research
Volume10
Issue number5
StatePublished - 1990
Externally publishedYes

Fingerprint

Osteoclasts
Interleukin-1
Interferons
Bone Marrow
Granulocyte-Macrophage Progenitor Cells
Bone Resorption
Calcitriol
Bone Remodeling
Granulocyte-Macrophage Colony-Stimulating Factor
Granulocytes
Macrophages
Cytokines
Escherichia coli
Phenotype
Growth

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

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title = "Interferons-α and -γ inhibit interleukin-1β-stimulated osteoclast-like cell formation in long-term human marrow cultures",
abstract = "Immune cell products can have major effects on bone remodelling. Cytokines, such as interleukin-1 (IL-1), are potent stimulators of bone resorption, whereas interferon-γ (IFN-γ) inhibits bone resorption stimulated by these factors. Bone resorption is a result of either increased numbers of osteoclasts, increased activity of individual osteoclasts, or both. Recently, we have shown that human recombinant IFN-γ is a potent inhibitor of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-induced formation of multinucleated cells (MNC) that express the osteoclast phenotype. However, it is unknown if other IFNs share this capacity to inhibit MNC formation. Therefore, we tested the effects of natural IFNs-α and -γ and Escherichia coli-derived recombinant human IFN-γ on MNC formation and on granulocyte-macrophage (CFU-GM) colony formation (an early osteoclast precursor) in human marrow cultures treated with IL-1β or CSF-GM, respectively, to determine their effects on human osteoclast formation. Each type of IFN inhibited CFU-GM colony formation similarly in a dose-dependent fashion, with 50{\%} inhibition seen at 64-250 U/ml. Natural or recombinant IFN-γ inhibited IL-1β-stimulated MNC formation in a dose-dependent manner with an ID50 of 1-16 U/ml. IFN-α was more potent that IFN-γ, with an ID50 of less than 1 U/ml. Furthermore, both IFN-α and -γ inhibited fusion of precursors of these multinucleated cells. These data demonstrate that IFNs-α and -γ inhibit MNC formation by inhibiting the growth of precursors for these cells as well as their subsequent fusion.",
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T1 - Interferons-α and -γ inhibit interleukin-1β-stimulated osteoclast-like cell formation in long-term human marrow cultures

AU - Kurihara, Noriyoshi

AU - Roodman, G. David

PY - 1990

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N2 - Immune cell products can have major effects on bone remodelling. Cytokines, such as interleukin-1 (IL-1), are potent stimulators of bone resorption, whereas interferon-γ (IFN-γ) inhibits bone resorption stimulated by these factors. Bone resorption is a result of either increased numbers of osteoclasts, increased activity of individual osteoclasts, or both. Recently, we have shown that human recombinant IFN-γ is a potent inhibitor of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-induced formation of multinucleated cells (MNC) that express the osteoclast phenotype. However, it is unknown if other IFNs share this capacity to inhibit MNC formation. Therefore, we tested the effects of natural IFNs-α and -γ and Escherichia coli-derived recombinant human IFN-γ on MNC formation and on granulocyte-macrophage (CFU-GM) colony formation (an early osteoclast precursor) in human marrow cultures treated with IL-1β or CSF-GM, respectively, to determine their effects on human osteoclast formation. Each type of IFN inhibited CFU-GM colony formation similarly in a dose-dependent fashion, with 50% inhibition seen at 64-250 U/ml. Natural or recombinant IFN-γ inhibited IL-1β-stimulated MNC formation in a dose-dependent manner with an ID50 of 1-16 U/ml. IFN-α was more potent that IFN-γ, with an ID50 of less than 1 U/ml. Furthermore, both IFN-α and -γ inhibited fusion of precursors of these multinucleated cells. These data demonstrate that IFNs-α and -γ inhibit MNC formation by inhibiting the growth of precursors for these cells as well as their subsequent fusion.

AB - Immune cell products can have major effects on bone remodelling. Cytokines, such as interleukin-1 (IL-1), are potent stimulators of bone resorption, whereas interferon-γ (IFN-γ) inhibits bone resorption stimulated by these factors. Bone resorption is a result of either increased numbers of osteoclasts, increased activity of individual osteoclasts, or both. Recently, we have shown that human recombinant IFN-γ is a potent inhibitor of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-induced formation of multinucleated cells (MNC) that express the osteoclast phenotype. However, it is unknown if other IFNs share this capacity to inhibit MNC formation. Therefore, we tested the effects of natural IFNs-α and -γ and Escherichia coli-derived recombinant human IFN-γ on MNC formation and on granulocyte-macrophage (CFU-GM) colony formation (an early osteoclast precursor) in human marrow cultures treated with IL-1β or CSF-GM, respectively, to determine their effects on human osteoclast formation. Each type of IFN inhibited CFU-GM colony formation similarly in a dose-dependent fashion, with 50% inhibition seen at 64-250 U/ml. Natural or recombinant IFN-γ inhibited IL-1β-stimulated MNC formation in a dose-dependent manner with an ID50 of 1-16 U/ml. IFN-α was more potent that IFN-γ, with an ID50 of less than 1 U/ml. Furthermore, both IFN-α and -γ inhibited fusion of precursors of these multinucleated cells. These data demonstrate that IFNs-α and -γ inhibit MNC formation by inhibiting the growth of precursors for these cells as well as their subsequent fusion.

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