|
|
Blood, 1 August 2005, Vol. 106, No. 3, pp. 852-859.
Prepublished online as a Blood First Edition Paper on April 7, 2005; DOI 10.1182/blood-2004-09-3662.
 Previous Article | Table of Contents | Next Article 
HEMATOPOIESIS
A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation
Na Kyung Lee,
Young Geum Choi,
Ji Youn Baik,
Song Yi Han,
Dae-won Jeong,
Yun Soo Bae,
Nacksung Kim, and
Soo Young Lee
From the Division of Molecular Life Sciences and Center for Cell Signaling Research, Ewha Womans University, Seoul, Korea; Brain Korea 21, Human Life Sciences, Seoul National University, Seoul, Korea; and the Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju, Korea.
Signaling by receptor activator of NF- B (nuclear factor-B) 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-acetylcysteine (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.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
Y. Wittrant, Y. Gorin, S. Mohan, B. Wagner, and S. L. Abboud-Werner
Colony-Stimulating Factor-1 (CSF-1) Directly Inhibits Receptor Activator of Nuclear Factor-{kappa}B Ligand (RANKL) Expression by Osteoblasts
Endocrinology,
November 1, 2009;
150(11):
4977 - 4988.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-H. Lee, H.-N. Kim, D. Yang, K. Jung, H.-M. Kim, H.-H. Kim, H. Ha, and Z. H. Lee
Trolox Prevents Osteoclastogenesis by Suppressing RANKL Expression and Signaling
J. Biol. Chem.,
May 15, 2009;
284(20):
13725 - 13734.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Lorenzo, M. Horowitz, and Y. Choi
Osteoimmunology: Interactions of the Bone and Immune System
Endocr. Rev.,
June 1, 2008;
29(4):
403 - 440.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. L. M. Sutton, X. Zhang, D. R. Dowd, Y. P. Kharode, B. S. Komm, and P. N. MacDonald
Semaphorin 3B Is a 1,25-Dihydroxyvitamin D3-Induced Gene in Osteoblasts that Promotes Osteoclastogenesis and Induces Osteopenia in Mice
Mol. Endocrinol.,
June 1, 2008;
22(6):
1370 - 1381.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. Ding, T. Jin, Z. Wang, and Y. Chen
Catalase potentiates retinoic acid-induced THP-1 monocyte differentiation into macrophage through inhibition of peroxisome proliferator-activated receptor {gamma}
J. Leukoc. Biol.,
June 1, 2007;
81(6):
1568 - 1576.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Orient, A. Donko, A. Szabo, T. L. Leto, and M. Geiszt
Novel sources of reactive oxygen species in the human body
Nephrol. Dial. Transplant.,
May 1, 2007;
22(5):
1281 - 1288.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Bedard and K.-H. Krause
The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology
Physiol Rev,
January 1, 2007;
87(1):
245 - 313.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Zhou, D. Immel, C.-X. Xi, A. Bierhaus, X. Feng, L. Mei, P. Nawroth, D. M. Stern, and W.-C. Xiong
Regulation of osteoclast function and bone mass by RAGE
J. Exp. Med.,
April 17, 2006;
203(4):
1067 - 1080.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Y. Han, N. K. Lee, K. H. Kim, I. W. Jang, M. Yim, J. H. Kim, W. J. Lee, and S. Y. Lee
Transcriptional induction of cyclooxygenase-2 in osteoclast precursors is involved in RANKL-induced osteoclastogenesis
Blood,
August 15, 2005;
106(4):
1240 - 1245.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
