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Fucoidan, a sulfated polysaccharide, inhibits osteoclast differentiation and function by modulating RANKL signaling.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2014 Oct 20; Vol. 15 (10), pp. 18840-55. Date of Electronic Publication: 2014 Oct 20. - Publication Year :
- 2014
-
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.
- Subjects :
- Animals
Bone Resorption drug therapy
Bone Resorption genetics
Bone Resorption metabolism
Cells, Cultured
Gene Expression Regulation drug effects
Mice
Mitogen-Activated Protein Kinases metabolism
NF-kappa B metabolism
Cell Differentiation drug effects
Osteoclasts cytology
Osteoclasts drug effects
Polysaccharides pharmacology
RANK Ligand metabolism
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 15
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 25334060
- Full Text :
- https://doi.org/10.3390/ijms151018840