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Interleukin-33 stimulates formation of functional osteoclasts from human CD14+ monocytes

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Abstract

Interleukin (IL)-33 is a recently described pro-inflammatory cytokine. Here we demonstrate IL-33 as a regulator of functional osteoclasts (OCs) from human CD14+ monocytes. IL-33 stimulates formation of tartrate-resistant acid phosphatase (TRAP)+ multinuclear OCs from monocytes. This action was suppressed by anti-ST2 antibody, suggesting that IL-33 acts through its receptor ST2, but not by the receptor activator of NF-κB ligand (RANKL) decoy, osteoprotegerin, or anti-RANKL antibody. IL-33 stimulated activating phosphorylations of signaling molecules in monocytes that are critical for OC development. These included Syk, phospholipase Cγ2, Gab2, MAP kinases, TAK-1, and NF-κB. IL-33 also enhanced expression of OC differentiation factors including TNF-α receptor-associated factor 6 (TRAF6), nuclear factor of activated T cells cytoplasmic 1, c-Fos, c-Src, cathepsin K, and calcitonin receptor. IL-33 eventually induced bone resorption. This study suggests that the osteoclastogenic property of IL-33 is mediated through TRAF6 as well as the immunoreceptor tyrosine-based activation motif-dependent Syk/PLCγ pathway in human CD14+ monocytes.

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Acknowledgments

This work was supported by the Konkuk University and partly by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) (No. 2009-0077125) and the grant of the Korean Ministry of Education, Science and Technology (The Regional Core Research Program/Chungbuk BIT Research-Oriented University Consortium). Dr. Michael A. Beaven was supported by the Intramural Program of the National Heart, Lung, and Blood Institute, National Institutes of Health.

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Authors and Affiliations

  1. College of Medicine, Institute of Biomedical Sciences and Technology, Konkuk University, Chungju, 380-701, Korea

    Se Hwan Mun, Na Young Ko, Hyuk Soon Kim, Jie Wan Kim, Do Kyun Kim, A-Ram Kim, Seung Hyun Lee, Bo Kyung Kim & Wahn Soo Choi

  2. Division of Rheumatology, College of Medicine, University of Ulsan, Seoul, 138-736, Korea

    Yong-Gil Kim & Chang Keun Lee

  3. Department of Oral Microbiology and Immunology, Wonkwang University School of Dentistry, Iksan, 570-749, Korea

    Seoung Hoon Lee

  4. Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Michael A. Beaven

  5. College of Pharmacy, Duksung Women’s University, Seoul, 132-714, Korea

    Young Mi Kim

  6. Department of Immunology, College of Medicine, Konkuk University, Chungju, 380-701, Korea

    Wahn Soo Choi

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  1. Se Hwan Mun
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Correspondence to Wahn Soo Choi.

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S. H. Mun, N. Y. Ko, and H.S. Kim equally contributed to this work.

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Mun, S.H., Ko, N.Y., Kim, H.S. et al. Interleukin-33 stimulates formation of functional osteoclasts from human CD14+ monocytes. Cell. Mol. Life Sci. 67, 3883–3892 (2010). https://doi.org/10.1007/s00018-010-0410-y

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