title: Genistein inhibits osteoclastic differentiation of RAW 264.7 cells via regulation of ROS production and scavenging.
abstract: Genistein, a phytoestrogen, has been demonstrated to have a bone-sparing and antiresorptive effect. Genistein can inhibit the osteoclast formation of receptor activator of nuclear factor-κB ligand (RANKL)-induced RAW 264.7 cells by preventing the translocation of nuclear factor-κB (NF-κB), a redox-sensitive factor, to the nucleus. Therefore, the suppressive effect of genistein on the reactive oxygen species (ROS) level during osteoclast differentiation and the mechanism associated with the control of ROS levels by genistein were investigated. The cellular antioxidant capacity and inhibitory effect of genistein were confirmed. The translation and activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (Nox1), as well as the disruption of the mitochondrial electron transport chain system were obviously suppressed by genistein in a dose-dependent manner. The induction of phase II antioxidant enzymes, such as superoxide dismutase 1 (SOD1) and heme oxygenase-1 (HO-1), was enhanced by genistein. In addition, the translational induction of nuclear factor erythroid 2-related factor 2 (Nrf2) was notably increased by genistein. These results provide that the inhibitory effects of genistein on RANKL-stimulated osteoclast differentiation is likely to be attributed to the control of ROS generation through suppressing the translation and activation of Nox1 and the disruption of the mitochondrial electron transport chain system, as well as ROS scavenging through the Nrf2-mediated induction of phase II antioxidant enzymes, such as SOD1 and HO-1.
authors.affiliation: Department of Food and Nutrition, Hannam University, Daejeon 305-811, Korea. blackbean10@naver.com.
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Food and Nutrition, Hannam University, Daejeon 305-811, Korea. kikkne@naver.com.
authors.forename: Jin-Kyoung
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Food and Nutrition, Hannam University, Daejeon 305-811, Korea. haedong@hnu.kr.
authors.forename: Hae-Dong
authors.initials: HD
authors.lastname: Jang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D004579:Electron Transport; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology; D019833:Genistein / Q000737:chemistry* / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D000074624:NADPH Oxidase 1; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects; D053245:RANK Ligand / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1
chemical_list: D016166:Free Radical Scavengers; D051267:NF-E2-Related Factor 2; D053245:RANK Ligand; D017382:Reactive Oxygen Species; C000606290:SOD1 protein, human; D019833:Genistein; D051547:Heme Oxygenase-1; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; C000614711:NOX1 protein, mouse