The Inhibitory Effect of Interleukin-10 on Mouse Osteoclast Formation Involves Novel Tyrosine-Phosphorylated Proteins

Authors

  • Mei Hua Hong,

    Corresponding author
    1. Department of Endocrine Research, Ligand Pharmaceuticals, Inc., San Diego, California, U.S.A.
    • Dr. Mei Hua Hong, Department of Endocrine Research Ligand Pharmaceuticals, Inc. 10275 Science Center Drive San Diego, CA 92121, U.S.A.
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  • Hilde Williams,

    1. Department of Endocrine Research, Ligand Pharmaceuticals, Inc., San Diego, California, U.S.A.
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  • Cheng He Jin,

    1. Department of Endocrine Research, Ligand Pharmaceuticals, Inc., San Diego, California, U.S.A.
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  • J. Wesley Pike

    Current affiliation:
    1. Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio, U.S.A.
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Abstract

Interleukin-10 (IL-10) inhibits osteoclast (OC) formation in rat and mouse systems. However, little is known concerning the mechanism of this inhibitory effect. Using a coculture system of mouse bone marrow cells and primary osteoblastic cells (POB), we evaluated the potential target cells for IL-10 and components of the IL-10 activating pathway. In the coculture system, IL-10 treatment abolished OC differentiation in a dose-dependent manner. This inhibitory effect occurred regardless of the stage of cellular proliferation and differentiation, suggesting that IL-10 may act on a variety of genes participating in OC formation. IL-10 specifically abrogated the production of IL-6 by enriched bone marrow-derived mononuclear cells (BMM) but not by osteoblastic cells. IL-10 treatment also stimulated the binding of a protein in the BMM to an IL-10 response element, whereas no such activation was induced in osteoblastic cells. In contrast, interferon γ (IFN-γ), another inhibitory factor, stimulated tyrosine-phosphorylated proteins to bind to an IL-10 response element in both monocytes and osteoblastic cells. These data suggest that the BMM are the direct target of IL-10 action. Importantly, oligonucleotide-specific precipitation confirmed that IL-10 treatment strongly augmented 88,85, and 70 kDa tyrosine-phosphorylated proteins in BMM. Taken together, these data show that IL-10 inhibits mouse OC formation by acting directly on hemopoietic OC precursor, through a novel signal transduction and activation pathway. (J Bone Miner Res 2000;15:911–918)

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