title: Effects of Nrf2 deficiency on bone microarchitecture in an experimental model of osteoporosis.
abstract: OBJECTIVE
  Redox imbalance contributes to bone fragility. We have evaluated the in vivo role of nuclear factor erythroid derived 2-related factor-2 (Nrf2), an important regulator of cellular responses to oxidative stress, in bone metabolism using a model of postmenopausal osteoporosis.
  
  
  METHODS
  Ovariectomy was performed in both wild-type and mice deficient in Nrf2 (Nrf2(-/-)). Bone microarchitecture was analyzed by μCT. Serum markers of bone metabolism were also measured. Reactive oxygen species production was determined using dihydrorhodamine 123.
  
  
  RESULTS
  Sham-operated or ovariectomized Nrf2(-/-) mice exhibit a loss in trabecular bone mineral density in femur, accompanied by a reduction in cortical area in vertebrae. Nrf2 deficiency tended to increase osteoblastic markers and significantly enhanced osteoclastic markers in sham-operated animals indicating an increased bone turnover with a main effect on bone resorption. We have also shown an increased production of oxidative stress in bone marrow-derived cells from sham-operated or ovariectomized Nrf2(-/-) mice and a higher responsiveness of bone marrow-derived cells to osteoclastogenic stimuli in vitro.
  
  
  CONCLUSIONS
  We have demonstrated in vivo a key role of Nrf2 in the maintenance of bone microarchitecture.
authors.affiliation: Department of Pharmacology, University of Valencia, Avenue Vicent A. Estellés s/n, Burjasot, 46100 Valencia, Spain.
authors.forename: Lidia
authors.initials: L
authors.lastname: Ibáñez
authors.affiliation: Department of Pharmacology, University of Valencia, Avenue Vicent A. Estellés s/n, Burjasot, 46100 Valencia, Spain.
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Ferrándiz
authors.affiliation: Department of Pharmacology, University of Valencia, Avenue Vicent A. Estellés s/n, Burjasot, 46100 Valencia, Spain.
authors.forename: Rita
authors.initials: R
authors.lastname: Brines
authors.affiliation: Trabeculae S.L., Parque Tecnolóxico de Galicia, San Cibrao das Viñas, 32900 Ourense, Spain.
authors.forename: David
authors.identifier: 0000-0002-8742-8223
authors.initials: D
authors.lastname: Guede
authors.affiliation: Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Department of Biochemistry and Alberto Sols Biomedical Research Institute UAM-CSIC, Faculty of Medicine, Autonomous University of Madrid, Avenue Arzobispo Morcillo 4, 28029 Madrid, Spain.
authors.forename: Antonio
authors.identifier: 0000-0002-4039-7140
authors.initials: A
authors.lastname: Cuadrado
authors.affiliation: Department of Pharmacology, University of Valencia, Avenue Vicent A. Estellés s/n, Burjasot, 46100 Valencia, Spain.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Alcaraz
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005269:Femur / Q000737:chemistry / Q000000981:diagnostic imaging / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000172:deficiency / Q000235:genetics*; D010010:Osteoclasts / Q000166:cytology; D010024:Osteoporosis / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D017382:Reactive Oxygen Species