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.