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RESEARCH PRODUCT

Effects of Nrf2 deficiency on bone microarchitecture in an experimental model of osteoporosis

María Luisa FerrándizAntonio CuadradoRita BrinesDavid GuedeMaría José AlcarazLidia Ibáñez

subject

Agingmedicine.medical_specialtycytoarchitectureArticle SubjectNF-E2-Related Factor 2MedicinaOsteoporosisOsteoclastsBone Marrow Cellsprotein deficiencymedicine.disease_causeenvironment and public healthBiochemistryBone resorptionBone remodelingMiceIn vivoInternal medicinemedicineAnimalsFemurcontrolled studyFemurlcsh:QH573-671Cells CulturedMice Knockoutchemistry.chemical_classificationReactive oxygen specieslcsh:CytologyChemistrybone densityCell DifferentiationCell BiologyGeneral Medicinerespiratory systemmedicine.diseaseosteoporosisMice Inbred C57BLDisease Models AnimalOxidative StressEndocrinologyOvariectomized ratReactive Oxygen SpeciesTomography X-Ray ComputedBiomarkersOxidative stressResearch Article

description

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

yearjournalcountryeditionlanguage
2014-02-03
http://hdl.handle.net/10486/667013