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A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation

Title
A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation
Authors
Lee N.K.Choi Y.G.Baik J.Y.Han S.Y.Jeong D.-W.Bae Y.S.Kim N.Lee S.Y.
Ewha Authors
배윤수이수영
SCOPUS Author ID
배윤수scopus; 이수영scopusscopus
Issue Date
2005
Journal Title
Blood
ISSN
0006-4971JCR Link
Citation
Blood vol. 106, no. 3, pp. 852 - 859
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Signaling by receptor activator of NF-κB (nuclear factor-κB) ligand (RANKL) is essential for differentiation of bone marrow monocyte-macrophage lineage (BMM) cells into osteoclasts. Here, we show RANKL stimulation of BMM cells transiently increased the intracellular level of reactive oxygen species (ROS) through a signaling cascade involving TNF (tumor necrosis factor) receptor-associated factor (TRAF) 6, Rac1, and NADPH (nicotinamide adenine dinucleotide phosphate) oxidase (Nox)1. A deficiency in TRAF6 or expression of a dominant-interfering mutant of TRAF6 blocks RANKL-mediated ROS production. Application of N-acetyl-cysteine (NAC) or blocking the activity of Nox, a protein leading to the formation of ROS, with diphenylene iodonium (DPI) inhibits the responses of BMM cells to RANKL, including ROS production, activation of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein (MAP) kinase, and extracellular signal-regulated kinase (ERK), and osteoclast differentiation. Moreover, both RANKL-mediated ROS production and osteoclast differentiation were completely blocked in precursors depleted of Nox1 activity by RNA interference or by expressing a dominant-negative mutant of Rac1. Together, these results indicate that ROSs act as an intracellular signal mediator for osteoclast differentiation. © 2005 by The American Society of Hematology.
DOI
10.1182/blood-2004-09-3662
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자연과학대학 > 생명과학전공 > Journal papers
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