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Effects of Mouse Hepcidin 1 Treatment on Osteoclast Differentiation and Intracellular Iron Concentration

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Abstract

Hepcidin is a key player in the regulation of mammalian iron homeostasis. Because iron overload may be one of the causes of osteoporosis, hepcidin may have therapeutic potential for osteoporosis patients. However, the effects of hepcidin on bone metabolism are not fully clear. We recently found that hepcidin can increase intracellular iron and calcium levels and promote mineralization in osteoblasts. The present study was designed to evaluate the effects of hepcidin on osteoclasts. Our results showed that mouse hepcidin 1 (MH1) can increase the number of TRAP-positive MNCs concomitant in both bone marrow-derived macrophages (BMMs) and RAW264.7 cells and upregulate mRNA levels of TRAP, cathepsin K, and MMP-9 and increase TRAP-5b protein secretion in RAW264.7 cells. Moreover, MH1 can downregulate the level of FPN1 protein and increase intracellular iron in RAW 264.7 cells. Therefore, we conclude that MH1 can significantly facilitate osteoclast differentiation in vitro. The mechanism behind accelerated differentiation may be associated with increased levels of intracellular iron. These findings may facilitate understanding of the effects of hepcidin on bone metabolism.

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Abbreviations

MH1:

Mouse hepcidin 1

BMMs:

Bone marrow-derived macrophages

M-CSF:

Macrophage colony-stimulating factor

RANKL:

Receptor Activator of Nuclear Factor κ B Ligand

TRAP:

Tartrate-resistant acid phosphatase

CTK:

Cathepsin K

MMP-9:

Matrix metalloproteinase 9

RT-PCR:

Reverse transcriptase polymerase chain reaction

FPN1:

Ferroportin 1

CLSM:

Confocal laser scanning microscope

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Acknowledgments

This work was partially supported by the National Natural Science Foundation of China (No. 81273090), Jiangsu provincial grant (No. BK2012608), Social Development Fund of Jiangsu Province (No. BE2011605), and Science and Technology Support Project of Zhenjiang City (social development 2014, to Guo-yang Zhao).

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Authors and Affiliations

  1. Department of Orthopaedics, The Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, China

    Guo-yang Zhao, Dong-hua Di & Bo Wang

  2. Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China

    You-jia Xu

  3. Department of Environmental Medicine, College of Medicine, The New York University, New York, NY, 10016, USA

    Xi Huang

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  1. Guo-yang Zhao
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  2. Dong-hua Di
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Correspondence to You-jia Xu.

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Zhao, Gy., Di, Dh., Wang, B. et al. Effects of Mouse Hepcidin 1 Treatment on Osteoclast Differentiation and Intracellular Iron Concentration. Inflammation 38, 718–727 (2015). https://doi.org/10.1007/s10753-014-9982-2

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