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Int. J. Mol. Sci. 2014, 15(10), 18840-18855; doi:10.3390/ijms151018840

Fucoidan, a Sulfated Polysaccharide, Inhibits Osteoclast Differentiation and Function by Modulating RANKL Signaling

1
Department of Orthopedic Surgery, Kyungpook National University School of Medicine, Daegu 700-422, Korea
2
Department of Food Science & Biotechnology, Kyungpook National University, Daegu 702-701, Korea
3
Food & Bio-Industry Research Institute, Kyungpook National University, Daegu 702-701, Korea
4
Skeletal Diseases Genome Research Center, Kyungpook National University, Daegu 700-721, Korea
5
Biomedical Research Institute, Kyungpook National University Hospital, Daegu 700-721, Korea
*
Authors to whom correspondence should be addressed.
Received: 7 August 2014 / Revised: 28 September 2014 / Accepted: 9 October 2014 / Published: 20 October 2014
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells 2014)
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Abstract

Multinucleated osteoclasts differentiate from hematopoietic progenitors of the monocyte/macrophage lineage. Because of its pivotal role in bone resorption, regulation of osteoclast differentiation is a potential therapeutic approach to the treatment of erosive bone disease. In this study, we have found that fucoidan, a sulfated polysaccharide extracted from brown seaweed, inhibited osteoclast differentiation. In particular, addition of fucoidan into the early stage osteoclast cultures significantly inhibited receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL)-induced osteoclast formation, thus suggesting that fucoidan affects osteoclast progenitors. Furthermore, fucoidan significantly inhibited the activation of RANKL-dependent mitogen-activated protein kinases (MAPKs) such as JNK, ERK, and p38, and also c-Fos and NFATc1, which are crucial transcription factors for osteoclastogenesis. In addition, the activation of NF-κB, which is an upstream transcription factor modulating NFATc1 expression, was alleviated in the fucoidan-treated cells. These results collectively suggest that fucoidan inhibits osteoclastogenesis from bone marrow macrophages by inhibiting RANKL-induced p38, JNK, ERK and NF-κB activation, and by downregulating the expression of genes that partake in both osteoclast differentiation and resorption. View Full-Text
Keywords: fucoidan; osteoclastogenesis; sulfated polysaccharide; bone resorption; RANKL (receptor activator of nuclear factor kappa B (NF-κB) ligand) fucoidan; osteoclastogenesis; sulfated polysaccharide; bone resorption; RANKL (receptor activator of nuclear factor kappa B (NF-κB) ligand)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Kim, Y.W.; Baek, S.-H.; Lee, S.-H.; Kim, T.-H.; Kim, S.-Y. Fucoidan, a Sulfated Polysaccharide, Inhibits Osteoclast Differentiation and Function by Modulating RANKL Signaling. Int. J. Mol. Sci. 2014, 15, 18840-18855.

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