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Mar Drugs. 2019 Jun 10;17(6). pii: E345. doi: 10.3390/md17060345.

Fucoidan Prevents RANKL-Stimulated Osteoclastogenesis and LPS-Induced Inflammatory Bone Loss via Regulation of Akt/GSK3β/PTEN/NFATc1 Signaling Pathway and Calcineurin Activity.

Lu SH1, Hsia YJ2, Shih KC3,4, Chou TC5,6,7,8.

Author information

1
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan. shooter741109512@gmail.com.
2
Dental Department and Devision of Oral and Maxillofacial Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan. yjhsia@yahoo.com.tw.
3
Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan. shihkc19610909@gmail.com.
4
Division of Endocrinology and Metabolism, Department of Internal Medicine, Cheng-Hsin General Hospital, Taipei 112, Taiwan. shihkc19610909@gmail.com.
5
Department of Biotechnology, Asia University, Taichung 413, Taiwan. chou195966@gmail.com.
6
China Medical University Hospital, China Medical University, Taichung 400, Taiwan. chou195966@gmail.com.
7
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan. chou195966@gmail.com.
8
Department of Pharmacology, National Defense Medical Center, Taipei 114, Taiwan. chou195966@gmail.com.

Abstract

Excessive osteoclast differentiation and/or function plays a pivotal role in the pathogenesis of bone diseases such as osteoporosis and rheumatoid arthritis. Here, we examined whether fucoidan, a sulfated polysaccharide present in brown algae, attenuates receptor activator of nuclear factor-κB ligand (RANKL)-stimulated osteoclastogenesis in vitro and lipopolysaccharide (LPS)-induced bone resorption in vivo, and investigated the molecular mechanisms involved. Our results indicated that fucoidan significantly inhibited osteoclast differentiation in RANKL-stimulated macrophages and the bone resorbing activity of osteoclasts. The effects of fucoidan may be mediated by regulation of Akt/GSK3β/PTEN signaling and suppression of the increase in intracellular Ca2+ level and calcineurin activity, thereby inhibiting the translocation of nuclear factor-activated T cells c1 (NFATc1) into the nucleus. However, fucoidan-mediated NFATc1 inactivation was greatly reversed by kenpaullone, a GSK3β inhibitor. In addition, using microcomputer tomography (micro-CT) scanning and bone histomorphometry, we found that fucoidan treatment markedly prevented LPS-induced bone erosion in mice. Collectively, we demonstrated that fucoidan was capable of inhibiting osteoclast differentiation and inflammatory bone loss, which may be modulated by regulation of Akt/GSK3β/PTEN/NFATc1 and Ca2+/calcineurin signaling cascades. These findings suggest that fucoidan may be a potential agent for the treatment of osteoclast-related bone diseases.

KEYWORDS:

RANKL; bone loss; calcineurin; fucoidan; lipopolysaccharide; osteoclastogenesis

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