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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
- 배윤수; 이수영
- SCOPUS Author ID
- 배윤수; 이수영
- Issue Date
- 2005
- Journal Title
- Blood
- ISSN
- 0006-4971
- Citation
- Blood vol. 106, no. 3, pp. 852 - 859
- Indexed
- SCI; SCIE; 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
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
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