title: Role of reactive oxygen species in angiotensin II: induced receptor activator of nuclear factor-κB ligand expression in mouse osteoblastic cells.
abstract: Angiotensin II (Ang II) has been shown to induce receptor activator of nuclear factor-κB ligand (RANKL) expression in osteoblasts associated with its effect on reactive oxygen species (ROS) production. The objective of the present study was to investigate the potential pathways by which Ang II induces RANKL expression and the role of ROS in Ang II-induced RANKL expression in mouse osteoblastic MC3T3-E1 cells. Treatment with Ang IIinduced RANKL expression in a dose- and time-dependent manner in osteoblasts, which was attenuated by pre-treatment with an AT1 receptor antagonist (olmesartan), ROS scavenger (N-acetylcysteine, NAC), or the ERK inhibitor (U0126), but not with AT2R antagonist (PD123319). Furthermore, Ang II enhanced AT1R and NAD(P)H oxidase (NOX) p22(phox) and p67(phox) expression and activity in osteoblasts. In addition, Ang II promoted ROS production, which was mitigated by pre-treatment with olmesartan or a NOX inhibitor (diphenyleneiodonium, DPI), but not with PD1123319 or U0126, in osteoblasts. Moreover, Ang II enhanced the ERK1/2 phosphorylation, which was abrogated by pre-treatment with olmesartan, NAC, DPI, or U0126 in osteoblasts. These results suggest that Ang II, through its AT1R, enhanced NOX activity and ROS production, and activated the ERK pathway to up-regulate RANKL expression in osteoblasts in vitro.
authors: Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China.
authors: Yanqiu
authors: Y
authors: Zhang
authors: Yongtao
authors: Y
authors: Zhang
authors: Jianqiang
authors: J
authors: Kou
authors: Chunsheng
authors: C
authors: Wang
authors: Kunzheng
authors: K
authors: Wang
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D057912:Angiotensin II Type 2 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D002460:Cell Line / Q000187:drug effects; D003573:Cytochrome b Group / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D057912:Angiotensin II Type 2 Receptor Blockers; D003573:Cytochrome b Group; D007093:Imidazoles; D010750:Phosphoproteins; D011725:Pyridines; D053245:RANK Ligand; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; C505689:Tnfsf11 protein, mouse; C079789:neutrophil cytosol factor 67K; D000804:Angiotensin II; C073402:PD 123319; D019255:NADPH Oxidases; C515614:Cyba protein, mouse; D048052:Mitogen-Activated Protein Kinase 3