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

**Jin-Woo Jeong 1, Seon Yeong Ji 2,3, Hyesook Lee 2,3, Su Hyun Hong 2,3, Gi-Young Kim 4, Cheol Park 5, Bae-Jin Lee 6, Eui Kyun Park 7, Jin Won Hyun 8, You-Jin Jeon 4 and Yung Hyun Choi 2,3,\***


Received: 2 July 2019; Accepted: 24 July 2019; Published: 26 July 2019

**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.

**Keywords:** fermented sea tangle; osteoclast differentiation; receptor of activator of nuclear factor kappa-B ligand (RANKL); nuclear factor-κB (NF-κB); reactive oxygen species (ROS)
