Abstract
Sea tangle (Laminaria japonica Aresch), a brown alga, has been used for many years as a functional food ingredient in the Asia-Pacific region. In the present study, we investigated the effects of fermented sea tangle extract (FST) on receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-stimulated osteoclast differentiation, using RAW 264.7 mouse macrophage cells. FST was found to inhibit the RANKL-stimulated activation of tartrate-resistance acid phosphatase (TRAP) and F-actin ring structure formation. FST also down-regulated the expression of osteoclast marker genes like TRAP, matrix metalloproteinase-9, cathepsin K and osteoclast-associated receptor by blocking RANKL-induced activation of NF-κB and expression of nuclear factor of activated T cells c1 (NFATc1), a master transcription factor. In addition, FST significantly abolished RANKL-induced generation of reactive oxygen species (ROS) by activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and its transcriptional targets. Hence, it seems likely that FST may have anti-osteoclastogenic potential as a result of its ability to inactivate the NF-κB-mediated NFATc1 signaling pathway and by reducing ROS production through activation of the Nrf2 pathway. Although further studies are needed to inquire its efficacy in vivo, FST appears to have potential use as an adjunctive or as a prophylactic treatment for osteoclastic bone disease.
Highlights
Bone remodeling is an active physiological process involving bone deposition and bone resorption by osteoblast and osteoclast, respectively
RAW 264.7 cells were treated with various concentrations of fermented sea tangle extract (FST) for 72 h and 3-(4,51Ashows that FST had no cytotoxicity on the cells at concentrations up to 800 μg/mL but relatively dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed
Our results demonstrated that RANKL promoted the degradation of IκB-α in the cytoplasm and induced the translocation of nuclear factor-κB (NF-κB) into the nucleus, both of which are essential for the activation of NF-κB but that these changes were completely inhibited by FST
Summary
Bone remodeling is an active physiological process involving bone deposition and bone resorption by osteoblast and osteoclast, respectively Imbalance of these processes in favor of resorption may lead to the formation of osteolytic lesions and an increase in bone disease-related disorders and morbidity [1,2,3]. A number of previous studies have shown that reactive oxygen species (ROS) are critical messengers for osteoclast differentiation [10,11] and increased activity of the Nrf signaling system can block this activation [12,13,14]. Various drugs have been used clinically to inhibit bone resorption, all have severe side effects when used long-term [15] and as a result, research into the prevention and treatment of osteolytic diseases using natural products has greatly increased in recent years
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