Abstract
In the osteopetrotic op/op mouse, the absence of macrophage colony-stimulating factor (M-CSF) prevents the growth of macrophages and osteoclasts and, consequently, bone resorption. In the present study, we investigated whether this deficiency in M-CSF production alters the production of cytokines in op/op bones. Calvariae of phenotypically normal (+/?) and op/op mice were stimulated in vitro with lipopolysaccharide or Pasteurella multocida toxin to produce cytokines. Interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) synthesis was the same both in calvaria from osteopetrotic and phenotypically normal animals. However, the production of granulocyte colony-stimulating factor (G-CSF), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF alpha) was lower in calvaria from op/op animals than was the case in +/? calvaria. Thus, the lack of biologically active M-CSF causes defects which are not compensated by cells independent of M-CSF.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / immunology
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Bacterial Toxins / toxicity
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Cell Division / drug effects
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Cell Division / physiology
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Cytokines / biosynthesis*
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Disease Models, Animal
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Female
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Granulocyte Colony-Stimulating Factor / biosynthesis
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Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
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Interleukin-3 / biosynthesis
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Interleukin-6 / biosynthesis
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Lipopolysaccharides / toxicity
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Macrophage Colony-Stimulating Factor / deficiency*
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Macrophage Colony-Stimulating Factor / genetics
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Macrophage Colony-Stimulating Factor / metabolism
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Macrophages / cytology
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Macrophages / drug effects
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Male
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Mice
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Osteoclasts / cytology
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Osteoclasts / drug effects
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Osteopetrosis / genetics
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Osteopetrosis / metabolism*
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Osteopetrosis / physiopathology
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Skull / drug effects
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Skull / metabolism*
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Tumor Necrosis Factor-alpha / biosynthesis
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Tumor Necrosis Factor-alpha / immunology
Substances
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Antibodies, Monoclonal
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Bacterial Toxins
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Cytokines
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Interleukin-3
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Interleukin-6
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Lipopolysaccharides
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Tumor Necrosis Factor-alpha
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Granulocyte Colony-Stimulating Factor
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Macrophage Colony-Stimulating Factor
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Granulocyte-Macrophage Colony-Stimulating Factor