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This study shows how skullcapflavone II (SFII), a flavonoid with anti\u2010inflammatory activity, regulates osteoclast differentiation, survival, and function. SFII inhibited osteoclastogenesis with decreased activation of MAPKs, Src, and cAMP response element\u2013binding protein (CREB), which have been known to be redox sensitive. SFII decreased reactive oxygen species by scavenging them or activating nuclear factor\u2010erythroid 2\u2013related factor 2 (Nrf2), and its effects were partially reversed by hydrogen peroxide cotreatment or Nrf2 deficiency. In addition, SFII attenuated survival, migration, and bone resorption, with a decrease in the expression of integrin \u03b2\n                    <jats:sub>3<\/jats:sub>\n                    , Src, and p130 Crk\u2010associated substrate, and the activation of RhoA and Rac1 in differentiated osteoclasts. Furthermore, SFII inhibited osteoclast formation and bone loss in an inflammation\u2010 or ovariectomy\u2010induced osteolytic mouse model. These findings suggest that SFII inhibits osteoclastogenesis through redox regulation of MAPKs, Src, and CREB and attenuates the survival and resorption function by modulating the integrin pathway in osteoclasts. SFII has therapeutic potential in the treatment and prevention of bone diseases caused by excessive osteoclast activity.\u2014Lee, J., Son, H. S., Lee, H. I., Lee, G.\u2010R., Jo, Y.\u2010J., Hong, S.\u2010E., Kim, N., Kwon, M., Kim, N. Y., Kim, H. J., Lee, Y. J., Seo, E. K., Jeong, W. Skullcapflavone II inhibits osteoclastogenesis by regulating reactive oxygen species and attenuates the survival and resorption function of osteoclasts by modulating integrin signaling. FASEB J. 33, 2026\u20132036 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201800866rr","type":"journal-article","created":{"date-parts":[[2018,9,14]],"date-time":"2018-09-14T14:04:52Z","timestamp":1536933892000},"page":"2026-2036","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Skullcapflavone II inhibits osteoclastogenesis by regulating reactive oxygen species and attenuates the survival and resorption function of osteoclasts by modulating integrin signaling"],"prefix":"10.1096","volume":"33","author":[{"given":"Jiae","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Life Science Research Center for Cellular Homeostasis Ewha Womans University Seoul South 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