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Regulation of osteoclast differentiation by the redox-dependent modulation of nuclear import of transcription factors
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Min, B-M | - |
dc.contributor.author | Huh, Y-J | - |
dc.contributor.author | Kim, J-M | - |
dc.contributor.author | Kim, H | - |
dc.contributor.author | Song, H | - |
dc.contributor.author | So, H | - |
dc.contributor.author | Lee, S Y | - |
dc.contributor.author | Kwon, S B | - |
dc.contributor.author | Kim, H J | - |
dc.contributor.author | Kim, H-H | - |
dc.contributor.author | Lee, S H | - |
dc.contributor.author | Choi, Y | - |
dc.contributor.author | Chung, S-C | - |
dc.contributor.author | Jeong, D-w | - |
dc.date.accessioned | 2010-09-02T07:21:19Z | - |
dc.date.available | 2010-09-02T07:21:19Z | - |
dc.date.issued | 2006 | - |
dc.identifier.citation | Cell Death and Differentiation 13:1138-1146 | en |
dc.identifier.issn | 1350-9047 | - |
dc.identifier.uri | https://hdl.handle.net/10371/69590 | - |
dc.description.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. | en |
dc.description.sponsorship | This study was supported by grant number 01-PJ5-PG1-01CH12-0002
from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (B-M Min). | en |
dc.language.iso | en | en |
dc.publisher | Nature Publishing Group | en |
dc.subject | reactive oxygen species (ROS) | en |
dc.subject | redox status | en |
dc.subject | GSH/GSSG ratio | en |
dc.subject | osteoclastogenesis | en |
dc.subject | RANKL-dependent signaling | en |
dc.title | Regulation of osteoclast differentiation by the redox-dependent modulation of nuclear import of transcription factors | en |
dc.type | Article | en |
dc.identifier.doi | 10.1038/sj.cdd.4401793 | - |
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