title: Fucoidan, a sulfated polysaccharide, inhibits osteoclast differentiation and function by modulating RANKL signaling.
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.
authors.affiliation: Department of Orthopedic Surgery, Kyungpook National University School of Medicine, Daegu 700-422, Korea. mujunggum2@lycos.co.kr.
authors.forename: Young Woo
authors.initials: YW
authors.lastname: Kim
authors.affiliation: Department of Orthopedic Surgery, Kyungpook National University School of Medicine, Daegu 700-422, Korea. sbaek@knu.ac.kr.
authors.forename: Seung-Hoon
authors.initials: SH
authors.lastname: Baek
authors.affiliation: Department of Food Science & Biotechnology, Kyungpook National University, Daegu 702-701, Korea. sang@knu.ac.kr.
authors.forename: Sang-Han
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Skeletal Diseases Genome Research Center, Kyungpook National University, Daegu 700-721, Korea. kimth0929@ynu.ac.kr.
authors.forename: Tae-Ho
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Orthopedic Surgery, Kyungpook National University School of Medicine, Daegu 700-422, Korea. syukim@knu.ac.kr.
authors.forename: Shin-Yoon
authors.initials: SY
authors.lastname: Kim
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects*; D011134:Polysaccharides / Q000494:pharmacology*; D053245:RANK Ligand / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D016328:NF-kappa B; D011134:Polysaccharides; D053245:RANK Ligand; C007789:fucoidan; D020928:Mitogen-Activated Protein Kinases