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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.

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


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.


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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