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

• Published in: International journal of molecular sciences Vol. 18; no. 12; p. 2635
• Main Authors: Ihn, Hye Jung, Kim, Ju Ang, Cho, Hye Sung, Shin, Hong-In, Kim, Gi-Young, Choi, Yung Hyun, Jeon, You-Jin, Park, Eui Kyun
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 06.12.2017; MDPI
• Subjects: Acid phosphatase; Acid phosphatase (tartrate-resistant); Acid resistance; Actin; Algae; Animals; Biocompatibility; Bone resorption; brown algae; Cathepsin K; Cathepsin K - genetics; Cathepsin K - metabolism; Cells, Cultured; Colony-stimulating factor; Dendritic cells; Differentiation; diphlorethohydroxycarmalol; Gene expression; Heterocyclic Compounds, 3-Ring - pharmacology; Kinases; Macrophage colony-stimulating factor; Macrophage Colony-Stimulating Factor - genetics; Macrophage Colony-Stimulating Factor - metabolism; Macrophages; Male; Mice; Mice, Inbred C57BL; NF-kappa B - genetics; NF-kappa B - metabolism; NF-κB; NF-κB protein; NFATC Transcription Factors - genetics; NFATC Transcription Factors - metabolism; osteoclast; Osteoclastogenesis; Osteoclasts - cytology; Osteoclasts - drug effects; Osteoclasts - metabolism; Osteogenesis - drug effects; Phaeophyceae - chemistry; Phosphorylation; Receptor Activator of Nuclear Factor-kappa B - genetics; Receptor Activator of Nuclear Factor-kappa B - metabolism; Signal Transduction; Tartrate-Resistant Acid Phosphatase - genetics; Tartrate-Resistant Acid Phosphatase - metabolism; TRANCE protein; NF-κB; diphlorethohydroxycarmalol; brown algae; osteoclast
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms18122635

Marine algae possess a variety of beneficial effects on human health. In this study, we investigated whether diphlorethohydroxycarmalol (DPHC), isolated from , 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.