Effects of Nrf2 deficiency on bone microarchitecture in an experimental model of osteoporosis
EntityUAM. Departamento de Bioquímica
PublisherHindawi Publishing Corporation
10.1155/2014/726590Oxidative Medicine and Cellular Longevity 2014 (2014): 726590
ISSN1942-0900 (print); 1942-0994 (online)
Funded byThis work was supported by grants SAF2010-22048, SAF2010-17822, RD12/0043/0013 (Ministerio de Economía y Competitividad, ISCIII, FEDER), and Prometeo2010-047 (Generalitat Valenciana). Lidia Ibáñez thanks Spanish Ministerio de Economía y Competitividad for a fellowship (FPI)
Subjectsbone density; controlled study; cytoarchitecture; osteoporosis; protein deficiency; Medicina
Rights© 2014 Lidia Ibáñez et al.
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.
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 CT. 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. Conclusion. We have demonstrated in vivo a key role of Nrf2 in the maintenance of bone microarchitecture
Google Scholar:Ibáñez, Lidia - Ferrándiz, María Luisa - Brines, Rita - Guede, David - Cuadrado Pastor, Antonio - Alcaraz, María José
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Transcription factor NRF2 as a therapeutic target for chronic diseases: A systems medicine approach Cuadrado Pastor, Antonio; Manda, Gina; Hassan, Ahmed; Alcaraz, María José; Barbas, Coral; Daiber, Andreas; Ghezzi, Pietro; León, Rafael; López, Manuela G.; Oliva, Baldo; Pajares, Marta; Rojo Sanchís, Ana Isabel; Robledinos-Antón, Natalia; Valverde, Ángela M.; Guney, Emre; Schmidt, Harald H.H.W.