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Oxid Med Cell Longev. 2014;2014:726590. doi: 10.1155/2014/726590. Epub 2014 Jul 7.

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

Author information

1
Department of Pharmacology, University of Valencia, Avenue Vicent A. Estellés s/n, Burjasot, 46100 Valencia, Spain.
2
Trabeculae S.L., Parque Tecnolóxico de Galicia, San Cibrao das Viñas, 32900 Ourense, Spain.
3
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.

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.

CONCLUSION:

We have demonstrated in vivo a key role of Nrf2 in the maintenance of bone microarchitecture.

PMID:
25120886
PMCID:
PMC4121150
DOI:
10.1155/2014/726590
[Indexed for MEDLINE]
Free PMC Article

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