A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation
| Autor: | Dae Won Jeong, Young Geum Choi, Yun Soo Bae, Na Kyung Lee, Song Yi Han, Nacksung Kim, Ji Youn Baik, Soo Young Lee |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
rac1 GTP-Binding Protein
musculoskeletal diseases MAP Kinase Signaling System Cellular differentiation Immunology Osteoclasts Bone Marrow Cells Biochemistry Monocytes Mice chemistry.chemical_compound Osteoclast medicine Animals Cell Lineage NADH NADPH Oxidoreductases TNF Receptor-Associated Factor 6 Membrane Glycoproteins Receptor Activator of Nuclear Factor-kappa B biology Kinase Macrophages Neuropeptides RANK Ligand Cell Differentiation Cell Biology Hematology rac GTP-Binding Proteins Cell biology Mice Inbred C57BL medicine.anatomical_structure chemistry RANKL Mitogen-activated protein kinase NADPH Oxidase 1 biology.protein Signal transduction Carrier Proteins Reactive Oxygen Species Nicotinamide adenine dinucleotide phosphate |
| Zdroj: | Blood. 106:852-859 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2004-09-3662 |
| Popis: | 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-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. |
| Databáze: | OpenAIRE |
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