title: NRROS Negatively Regulates Osteoclast Differentiation by Inhibiting RANKL-Mediated NF-N:B and Reactive Oxygen Species Pathways.
abstract: Negative regulator of reactive oxygen species (NRROS) is known to repress ROS generation in phagocytes. In this study, we examined the roles of NRROS in both osteoclasts and osteoblasts. Our results demonstrate that NRROS negatively regulates the differentiation of osteoclasts, but not osteoblasts. Further, overexpression of NRROS in osteoclast precursor cells attenuates RANKL-induced osteoclast differentiation. Conversely, osteoclast differentiation is enhanced upon siRNA-mediated knockdown of NRROS. Additionally, NRROS attenuates RANKL-induced NF-N:B activation, as well as degradation of the NOX1 and NOX2 proteins, which are required for ROS generation. Based on our observations, we present NRROS as a novel negative regulator of RANKL-induced osteoclastogenesis.
authors.affiliation: Department of Pharmacology, Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju 501-746, Korea.
authors.forename: Jung Ha
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju 501-746, Korea.
authors.forename: Kabsun
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju 501-746, Korea.
authors.forename: Inyoung
authors.initials: I
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju 501-746, Korea.
authors.forename: Semun
authors.initials: S
authors.lastname: Seong
authors.affiliation: Department of Pharmacology, Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju 501-746, Korea.
authors.forename: Nacksung
authors.initials: N
authors.lastname: Kim
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D053779:Latent TGF-beta Binding Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D000074624:NADPH Oxidase 1; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010006:Osteoblasts / Q000502:physiology; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology*; D061251:Primary Cell Culture; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D053779:Latent TGF-beta Binding Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D016328:NF-kappa B; C000589026:NRROS protein, mouse; D011506:Proteins; D053245:RANK Ligand; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D009247:NADH, NADPH Oxidoreductases; C488842:Cybb protein, mouse; D000074624:NADPH Oxidase 1; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C000614711:NOX1 protein, mouse
keywords: NRROS; RANKL; osteoclast differentiation