title: A crucial role for reactive oxygen species in macrophage colony-stimulating factor-induced RANK expression in osteoclastic differentiation.
abstract: Macrophage colony-stimulating factor (M-CSF) is essential for differentiation from hematopoietic precursor cells into osteoclasts. M-CSF transiently increased the intracellular level of reactive oxygen species (ROS) through an NADPH oxidase (Nox) and induced the expression of receptor for activation of nuclear factor-κB (RANK) in early-stage osteoclast precursor cells (c-fms+RANK-). Blocking of the activity of Nox with diphenylene iodonium inhibited ROS production, activation of extracellular signal-regulated kinase (ERK), and the expression of RANK, PU.1 and MITF. The suppression of Nox2, but not Nox1, expression by RNA interference inhibited ROS production and RANK expression. These results suggested that ROS produced in response to M-CSF via a process mediated by Nox2 acted as an intracellular signaling mediator for RANK expression through the activation of ERK and the expression of PU.1 and MITF in early-stage osteoclast precursor cells.
authors: Department of Food Science and Nutrition, Nara Women's University, Nara 630-8506, Japan.
authors: Atsuko
authors: A
authors: Nakanishi
authors: Mamiko
authors: M
authors: Hie
authors: Natsumi
authors: N
authors: Iitsuka
authors: Ikuyo
authors: I
authors: Tsukamoto
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009861:Onium Compounds / Q000494:pharmacology; D010010:Osteoclasts / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D007527:Isoenzymes; D009861:Onium Compounds; D017382:Reactive Oxygen Species; D053246:Receptor Activator of Nuclear Factor-kappa B; C007517:diphenyleneiodonium; D016173:Macrophage Colony-Stimulating Factor; D019255:NADPH Oxidases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one