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Diphlorethohydroxycarmalol from Ishige okamurae Suppresses Osteoclast Differentiation by Downregulating the NF-κB Signaling Pathway

Department of Oral Pathology and Regenerative Medicine, School of Dentistry, Institute for Hard Tissue and Biotooth Regeneration, Kyungpook National University, Daegu 41940, Korea
Department of Marine Life Science, Jeju National University, Jeju 63243, Korea
Department of Biochemistry, College of Oriental Medicine, Dong-Eui University, Busan 47227, Korea
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2017, 18(12), 2635;
Received: 2 November 2017 / Revised: 1 December 2017 / Accepted: 4 December 2017 / Published: 6 December 2017
(This article belongs to the Section Biochemistry)
PDF [2924 KB, uploaded 6 December 2017]


Marine algae possess a variety of beneficial effects on human health. In this study, we investigated whether diphlorethohydroxycarmalol (DPHC), isolated from Ishige okamurae, a brown alga, suppresses receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. DPHC significantly suppressed RANKL-induced osteoclast differentiation and macrophage-colony stimulating factor (M-CSF) expression in a dose-dependent manner. In addition, it significantly inhibited actin ring formation, the expression of osteoclast marker genes, such as tartrate-resistant acid phosphatase (TRAP), nuclear factor of activated T-cells cytoplasmic 1 (Nfatc1), cathepsin K (Ctsk), and dendritic cell-specific transmembrane protein (Dcstamp), and osteoclast-induced bone resorption. Analysis of the RANKL-mediated signaling pathway showed that the phosphorylation of both IκB and p65 was specifically inhibited by DPHC. These results suggest that DPHC substantially suppresses osteoclastogenesis by downregulating the RANK-NF-κB signaling pathway. Thus, it holds significant potential for the treatment of skeletal diseases associated with an enhanced osteoclast activity. View Full-Text
Keywords: diphlorethohydroxycarmalol; brown algae; osteoclast; NF-κB diphlorethohydroxycarmalol; brown algae; osteoclast; NF-κB

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Ihn, H.J.; Kim, J.A.; Cho, H.S.; Shin, H.-I.; Kim, G.-Y.; Choi, Y.H.; Jeon, Y.-J.; Park, E.K. Diphlorethohydroxycarmalol from Ishige okamurae Suppresses Osteoclast Differentiation by Downregulating the NF-κB Signaling Pathway. Int. J. Mol. Sci. 2017, 18, 2635.

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