Oncotarget

Research Papers:

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

Xiaoqing Zhu, Yinghua Zhao, Yuxue Jiang, Tianxue Qin, Jintong Chen, Xiao Chu, Qing Yi, Sujun Gao and Siqing Wang _

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Oncotarget. 2017; 8:53366-53374. https://doi.org/10.18632/oncotarget.18411

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Abstract

Xiaoqing Zhu1,4,*, Yinghua Zhao2,*, Yuxue Jiang2, Tianxue Qin1, Jintong Chen2, Xiao Chu2, Qing Yi2,3, Sujun Gao1 and Siqing Wang2

1Department of Hematology, The First Hospital of Jilin University, Changchun 130061, China

2Department of Cancer Immunology, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, China

3Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA

4Department of Hematology, Ningbo Hangzhou Bay Hospital, Ningbo 315336, China

*These authors have contributed equally to this work

Correspondence to:

Siqing Wang, email: siw1970@yahoo.com

Sujun Gao, email: sujung1963@sina.com

Keywords: osteoclast, dectin-1, NFATc1, IL-33, multiple myeloma

Received: January 02, 2016    Accepted: May 10, 2017    Published: June 08, 2017

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.


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