Fermented Sea Tangle (Laminaria japonica Aresch) Suppresses RANKL-Induced Osteoclastogenesis by Scavenging ROS in RAW 264.7 Cells

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.

Protection against Oxidative Stress-Induced Apoptosis by Fermented Sea Tangle (Laminaria japonica Aresch) in Osteoblastic MC3T3-E1 Cells through Activation of Nrf2 Signaling Pathway

“…Thus, the nuclear translocation after phosphorylation of Nrf2 implies that Nrf2 is activated for transcriptional activation of downstream enzymes, including HO-1, by binding to the AREs. Recently, we demonstrated that the activation of Nrf2 by FST contributed to the inhibition of osteoclastogenesis through blockade of oxidative stress [27]. Supporting this result, our data showed that FST could further activate Nrf2 in the presence of H 2 O 2 , as evidence for the predominant nuclear expression of p-Nrf2 in H 2 O 2 and FST-cotreated cells.…”

“…In addition, the application of FST is attracting attention as a potential tool to improve physiological functions such as memory improvement, anti-inflammatory, obesity reduction, and stress management [21,22,[24][25][26]. Recently, we reported that FST inhibited osteoclastogenesis, which was due to the blockade of oxidative stress involved in the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway [27]. However, the effects and mechanisms of FST in oxidative stress-induced osteoblast dysfunction remain unclear.…”

Protective Effect of Fermented Sea Tangle Extract on Skin Cell Damage Caused by Particulate Matter

“…FST extract was provided by Professor Young Hyun Choi of Dongeui University (Busan, Republic of Korea) 19 . Sea tangle was added to water at a ratio of 1:15 (w/v), and yeast extract and glucose were added according to the amount of sea tangle added.…”

The Mechanism of Nrf2/ARE Signaling Pathway in Periodontitis with Atherosclerosis

“…The excessive activation of osteoclasts is the main pathological response of periodontitis. Different scholars have found that the intracellular ROS level can be reduced and Nrf2/NF-κB/NFATc1 signaling pathway can be regulated to inhibit osteoclast formation and alveolar bone resorption by inducing the transcription of antioxidant genes mediated by Nrf2 [15,16]. Nrf2 is known to regulate osteoclast differentiation and function by decreasing ROS via induction of anti-oxidant enzymes, such as sulfiredoxin (Srx) and peroxiredoxin (Prx).…”