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Regulation of osteoclast differentiation by the redox-dependent modulation of nuclear import of transcription factors

Cited 49 time in Web of Science Cited 48 time in Scopus
Authors
Min, B-M; Huh, Y-J; Kim, J-M; Kim, H; Song, H; So, H; Lee, S Y; Kwon, S B; Kim, H J; Kim, H-H; Lee, S H; Choi, Y; Chung, S-C; Jeong, D-w
Issue Date
2006
Publisher
Nature Publishing Group
Citation
Cell Death and Differentiation 13:1138-1146
Keywords
reactive oxygen species (ROS)redox statusGSH/GSSG ratioosteoclastogenesisRANKL-dependent signaling
Abstract
This study sought to characterize the reduced glutathione (GSH)/oxidized GSSG ratio during osteoclast differentiation and determine whether changes in the intracellular redox status regulate its differentiation through a RANKL-dependent signaling pathway. A progressive decrease of the GSH/GSSG ratio was observed during osteoclast differentiation, and the phenomenon was dependent on a decrease in total glutathione via downregulation of expression of the -glutamylcysteinyl synthetase modifier gene. Glutathione depletion by L-buthionine-(S,R)-sulfoximine (BSO) was found to inhibit osteoclastogenesis by blocking nuclear import of NF-B and AP-1 in RANKL-propagated signaling and bone pit formation by increasing BSO concentrations in mature osteoclasts. Furthermore, intraperitoneal injection of BSO in mice resulted in an increase in bone density and a decrease of the number of osteoclasts in bone. Conversely, glutathione repletion with either N-acetylcysteine or GSH enhanced osteoclastogenesis. These findings indicate that redox status decreases during osteoclast differentiation and that this modification directly regulates RANKL-induced osteoclastogenesis.
ISSN
1350-9047
Language
English
URI
https://hdl.handle.net/10371/69590
DOI
https://doi.org/10.1038/sj.cdd.4401793
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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