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Oncotarget. 2017 Jun 8;8(32):53366-53374. doi: 10.18632/oncotarget.18411. eCollection 2017 Aug 8.

Dectin-1 signaling inhibits osteoclastogenesis via IL-33-induced inhibition of NFATc1.

Author information

1
Department of Hematology, The First Hospital of Jilin University, Changchun 130061, China.
2
Department of Hematology, Ningbo Hangzhou Bay Hospital, Ningbo 315336, China.
3
Department of Cancer Immunology, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, China.
4
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
#
Contributed equally

Abstract

Abnormal osteoclast activation contributes to osteolytic bone diseases (OBDs). It was reported that curdlan, an agonist of dectin-1, inhibits osteoclastogenesis. However, the underlying mechanisms are not fully elucidated. In this study, we found that curdlan potently inhibited RANKL-induced osteoclast differentiation and the resultant bone resorption. Curdlan inhibited the expression of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), the key transcriptional factor for osteoclastogenesis. Notably, dectin-1 activation increased the expression of MafB, an inhibitor of NFATc1, and IL-33 in osteoclast precursors. Mechanistic studies revealed that IL-33 enhanced the expression of MafB in osteoclast precursors and inhibited osteoclast precursors to differentiate into mature osteoclasts. Furthermore, blocking ST2, the IL-33 receptor, partially abrogated curdlan-induced inhibition of NFATc1 expression and osteoclast differentiation. Thus, our study has provided new insights into the mechanisms of dectin-1-induced inhibition of osteoclastogenesis and may provide new targets for the therapy of OBDs.

KEYWORDS:

IL-33; NFATc1; dectin-1; multiple myeloma; osteoclast

Conflict of interest statement

CONFLICTS OF INTEREST The authors have no financial conflicts of interest.

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