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

1
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan
2
Dental Department and Devision of Oral and Maxillofacial Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan
3
Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan
4
Division of Endocrinology and Metabolism, Department of Internal Medicine, Cheng-Hsin General Hospital, Taipei 112, Taiwan
5
Department of Biotechnology, Asia University, Taichung 413, Taiwan
6
China Medical University Hospital, China Medical University, Taichung 400, Taiwan
7
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan
8
Department of Pharmacology, National Defense Medical Center, Taipei 114, Taiwan
*
Author to whom correspondence should be addressed.
These authors have contributed equally to this work.
Mar. Drugs 2019, 17(6), 345; https://doi.org/10.3390/md17060345
Received: 20 May 2019 / Revised: 4 June 2019 / Accepted: 5 June 2019 / Published: 10 June 2019
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. View Full-Text
Keywords: fucoidan; RANKL; osteoclastogenesis; calcineurin; lipopolysaccharide; bone loss fucoidan; RANKL; osteoclastogenesis; calcineurin; lipopolysaccharide; bone loss
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Lu, S.-H.; Hsia, Y.-J.; Shih, K.-C.; Chou, T.-C. Fucoidan Prevents RANKL-Stimulated Osteoclastogenesis and LPS-Induced Inflammatory Bone Loss via Regulation of Akt/GSK3β/PTEN/NFATc1 Signaling Pathway and Calcineurin Activity. Mar. Drugs 2019, 17, 345.

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