Cellular and Molecular Life Sciences

, Volume 67, Issue 22, pp 3883–3892 | Cite as

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

  • Se Hwan Mun
  • Na Young Ko
  • Hyuk Soon Kim
  • Jie Wan Kim
  • Do Kyun Kim
  • A-Ram Kim
  • Seung Hyun Lee
  • Yong-Gil Kim
  • Chang Keun Lee
  • Seoung Hoon Lee
  • Bo Kyung Kim
  • Michael A. Beaven
  • Young Mi Kim
  • Wahn Soo Choi
Research Article


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.


Interleukin-33 Osteoclasts Differentiation Human CD14+ monocytes Bone resorption 



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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Copyright information

© Springer Basel AG 2010

Authors and Affiliations

  • Se Hwan Mun
    • 1
  • Na Young Ko
    • 1
  • Hyuk Soon Kim
    • 1
  • Jie Wan Kim
    • 1
  • Do Kyun Kim
    • 1
  • A-Ram Kim
    • 1
  • Seung Hyun Lee
    • 1
  • Yong-Gil Kim
    • 2
  • Chang Keun Lee
    • 2
  • Seoung Hoon Lee
    • 3
  • Bo Kyung Kim
    • 1
  • Michael A. Beaven
    • 4
  • Young Mi Kim
    • 5
  • Wahn Soo Choi
    • 1
    • 6
  1. 1.College of Medicine, Institute of Biomedical Sciences and TechnologyKonkuk UniversityChungjuKorea
  2. 2.Division of Rheumatology, College of MedicineUniversity of UlsanSeoulKorea
  3. 3.Department of Oral Microbiology and ImmunologyWonkwang University School of DentistryIksanKorea
  4. 4.Laboratory of Molecular Immunology, National Heart, Lung, and Blood InstituteNational Institutes of HealthBethesdaUSA
  5. 5.College of PharmacyDuksung Women’s UniversitySeoulKorea
  6. 6.Department of Immunology, College of MedicineKonkuk UniversityChungjuKorea

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