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.
Highlights
Adult bone mass is governed by tight regulation and balance between the osteoclast-mediated bone resorption and osteoblast-induced bone formation [1,2]
We examined whether fucoidan inhibits RANKL-induced osteoclast formation in bone marrow-derived macrophages (BMMs) cultures
macrophage colony-stimulating factor (M-CSF) together with or without various concentrations of fucoidan. Because both mononuclear osteoclast progenitor cells and osteoclast-like multinucleated cells (MNCs) are positive for tartrate-resistant acid phosphatase (TRAP), we examined whether fucoidan has any effect on the total TRAP activity and multinucleated cells (MNC)
Summary
Adult bone mass is governed by tight regulation and balance between the osteoclast-mediated bone resorption and osteoblast-induced bone formation [1,2]. When osteoclastic bone resorption exceeds bone formation, the resulting imbalance causes bone-destructive diseases such as osteoporosis and rheumatoid arthritis [3]. Current drugs for bone health include inhibitors of osteoclastic-mediated bone resorption such as bisphosphonates, calcitonin, and estrogen that help to maintain bone mass and reduce fractures [4,5]. These pharmacological treatments have serious side effects such as hypercalcemia, increased risk of breast and endometrial cancer, and gastrointestinal intolerance against bisphosphonate [6,7].
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