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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.
This article was published in the following journal.
Name: International journal of molecular sciences
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A humanized monoclonal antibody and an inhibitor of the RANK LIGAND, which regulates OSTEOCLAST differentiation and bone remodeling. It is used as a BONE DENSITY CONSERVATION AGENT in the treatment of OSTEOPOROSIS.
A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B and OSTEOPROTEGERIN. It plays an important role in regulating OSTEOCLAST differentiation and activation.
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A treatment that suppresses undesirable behavior by simultaneously exposing the subject to unpleasant consequences.
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