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During osteoclastogenesis, reactive oxygen species (\n                    <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>\n                    ) play a role in the intracellular signalling triggered by receptor activator of nuclear factor\u2010\u03baB ligand (\n                    <jats:styled-content style=\"fixed-case\">RANKL<\/jats:styled-content>\n                    ) stimulation. Previously, we demonstrated that induction of antioxidant enzymes by Nrf2 activation using\n                    <jats:italic>Nrf2<\/jats:italic>\n                    \u2010gene transfer, an\n                    <jats:styled-content style=\"fixed-case\">ETGE<\/jats:styled-content>\n                    \u2010peptide or polyphenols, successfully ameliorated\n                    <jats:styled-content style=\"fixed-case\">RANKL<\/jats:styled-content>\n                    \u2010dependent osteoclastogenesis. Dimethyl fumarate (\n                    <jats:styled-content style=\"fixed-case\">DMF<\/jats:styled-content>\n                    ) has been shown to activate Nrf2 signalling and has been lately used in clinical trials for neurodegenerative diseases. In this study, we hypothesized that Nrf2 activation by\n                    <jats:styled-content style=\"fixed-case\">DMF<\/jats:styled-content>\n                    would inhibit osteoclastogenesis and bone destruction\n                    <jats:italic>via<\/jats:italic>\n                    attenuation of intracellular\n                    <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>\n                    signalling through antioxidant mechanisms.\n                    <jats:styled-content style=\"fixed-case\">RAW<\/jats:styled-content>\n                    264.7 cells were used as osteoclast progenitor cells. We found that\n                    <jats:styled-content style=\"fixed-case\">DMF<\/jats:styled-content>\n                    induced Nrf2 translocation to the nucleus, augmented Nrf2 promoter\u2010luciferase reporter activity and increased antioxidant enzyme expression. Using flow cytometry, we found that\n                    <jats:styled-content style=\"fixed-case\">DMF<\/jats:styled-content>\n                    attenuated\n                    <jats:styled-content style=\"fixed-case\">RANKL<\/jats:styled-content>\n                    \u2010mediated intracellular\n                    <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>\n                    generation, which resulted in the inhibition of\n                    <jats:styled-content style=\"fixed-case\">RANKL<\/jats:styled-content>\n                    \u2010mediated osteoclastogenesis. Local\n                    <jats:styled-content style=\"fixed-case\">DMF<\/jats:styled-content>\n                    injection into the calvaria of male\n                    <jats:styled-content style=\"fixed-case\">BALB<\/jats:styled-content>\n                    \/c mice resulted in attenuated bone destruction in lipopolysaccharide\u2010treated mice. In conclusion, we demonstrated in a preclinical setting that\n                    <jats:styled-content style=\"fixed-case\">DMF<\/jats:styled-content>\n                    inhibited\n                    <jats:styled-content style=\"fixed-case\">RANKL<\/jats:styled-content>\n                    \u2010mediated osteoclastogenesis and bone destruction\n                    <jats:italic>via<\/jats:italic>\n                    induction of Nrf2\u2010mediated transcription of antioxidant genes and consequent decrease in intracellular\n                    <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>\n                    levels. Our results suggest that\n                    <jats:styled-content style=\"fixed-case\">DMF<\/jats:styled-content>\n                    may be a promising inhibitor of bone destruction in diseases like periodontitis, rheumatoid arthritis and osteoporosis.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.13367","type":"journal-article","created":{"date-parts":[[2017,10,24]],"date-time":"2017-10-24T03:12:38Z","timestamp":1508814758000},"page":"1138-1147","source":"Crossref","is-referenced-by-count":68,"title":["Dimethyl fumarate inhibits osteoclasts\n                    <i>via<\/i>\n                    attenuation of reactive oxygen species signalling by augmented antioxidation"],"prefix":"10.1111","volume":"22","author":[{"given":"Yuuki","family":"Yamaguchi","sequence":"first","affiliation":[{"name":"Department of Orthodontics School of Dental Medicine Tsurumi University Yokohama 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