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A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation.
Blood. 2005 Aug 01; 106(3):852-9.Blood

Abstract

Signaling by receptor activator of NF-kappaB (nuclear factor-kappaB) 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.

Authors+Show Affiliations

Division of Molecular Life Sciences and Center for Cell Signaling Research, Ewha Womans University, Seoul, 120-750, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15817678

Citation

Lee, Na Kyung, et al. "A Crucial Role for Reactive Oxygen Species in RANKL-induced Osteoclast Differentiation." Blood, vol. 106, no. 3, 2005, pp. 852-9.
Lee NK, Choi YG, Baik JY, et al. A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation. Blood. 2005;106(3):852-9.
Lee, N. K., Choi, Y. G., Baik, J. Y., Han, S. Y., Jeong, D. W., Bae, Y. S., Kim, N., & Lee, S. Y. (2005). A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation. Blood, 106(3), 852-9.
Lee NK, et al. A Crucial Role for Reactive Oxygen Species in RANKL-induced Osteoclast Differentiation. Blood. 2005 Aug 1;106(3):852-9. PubMed PMID: 15817678.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation. AU - Lee,Na Kyung, AU - Choi,Young Geum, AU - Baik,Ji Youn, AU - Han,Song Yi, AU - Jeong,Dae-Won, AU - Bae,Yun Soo, AU - Kim,Nacksung, AU - Lee,Soo Young, Y1 - 2005/04/07/ PY - 2005/4/9/pubmed PY - 2005/9/22/medline PY - 2005/4/9/entrez SP - 852 EP - 9 JF - Blood JO - Blood VL - 106 IS - 3 N2 - Signaling by receptor activator of NF-kappaB (nuclear factor-kappaB) 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. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/15817678/A_crucial_role_for_reactive_oxygen_species_in_RANKL_induced_osteoclast_differentiation_ L2 - https://ashpublications.org/blood/article-lookup/doi/10.1182/blood-2004-09-3662 DB - PRIME DP - Unbound Medicine ER -