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Genistein Inhibits Osteoclastic Differentiation of RAW 264.7 Cells via Regulation of ROS Production and Scavenging

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-s...

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Autores principales: Lee, Sang-Hyun, Kim, Jin-Kyoung, Jang, Hae-Dong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4100171/
https://www.ncbi.nlm.nih.gov/pubmed/24927148
http://dx.doi.org/10.3390/ijms150610605
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author Lee, Sang-Hyun
Kim, Jin-Kyoung
Jang, Hae-Dong
author_facet Lee, Sang-Hyun
Kim, Jin-Kyoung
Jang, Hae-Dong
author_sort Lee, Sang-Hyun
collection PubMed
description 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.
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spelling pubmed-41001712014-07-16 Genistein Inhibits Osteoclastic Differentiation of RAW 264.7 Cells via Regulation of ROS Production and Scavenging Lee, Sang-Hyun Kim, Jin-Kyoung Jang, Hae-Dong Int J Mol Sci Article 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. MDPI 2014-06-12 /pmc/articles/PMC4100171/ /pubmed/24927148 http://dx.doi.org/10.3390/ijms150610605 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Lee, Sang-Hyun
Kim, Jin-Kyoung
Jang, Hae-Dong
Genistein Inhibits Osteoclastic Differentiation of RAW 264.7 Cells via Regulation of ROS Production and Scavenging
title Genistein Inhibits Osteoclastic Differentiation of RAW 264.7 Cells via Regulation of ROS Production and Scavenging
title_full Genistein Inhibits Osteoclastic Differentiation of RAW 264.7 Cells via Regulation of ROS Production and Scavenging
title_fullStr Genistein Inhibits Osteoclastic Differentiation of RAW 264.7 Cells via Regulation of ROS Production and Scavenging
title_full_unstemmed Genistein Inhibits Osteoclastic Differentiation of RAW 264.7 Cells via Regulation of ROS Production and Scavenging
title_short Genistein Inhibits Osteoclastic Differentiation of RAW 264.7 Cells via Regulation of ROS Production and Scavenging
title_sort genistein inhibits osteoclastic differentiation of raw 264.7 cells via regulation of ros production and scavenging
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4100171/
https://www.ncbi.nlm.nih.gov/pubmed/24927148
http://dx.doi.org/10.3390/ijms150610605
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AT janghaedong genisteininhibitsosteoclasticdifferentiationofraw2647cellsviaregulationofrosproductionandscavenging