Nrf2 epigenetic derepression induced by running exercise protects against osteoporosis

This study investigates the epigenetic mechanisms by which running exercise protects against osteoporosis. The researchers found that epigenetic derepression of Nrf2, a key regulator of oxidative stress, mediates the osteoprotective effects of running in an ovariectomized mouse model of osteoporosis. Nrf2 gene knockout mice exhibited worse bone mineral density reduction, highlighting Nrf2's anti-osteoporotic role. Femoral Nrf2 was repressed in osteoporotic patients and mice, associated with increased DNA methyltransferases (Dnmts) and Nrf2 promoter hypermethylation. Running exercise corrected these epigenetic alterations, recovering Nrf2 expression and improving bone mass and microstructure. The osteoprotective effects of running were largely abolished in Nrf2 knockout mice, confirming Nrf2's crucial role in mediating the benefits of exercise.

Xingren Chen, Xiaobo Zhu, Ai Wei, Fang Chen, Qi Gao, Ke Lu, Qing Jiang, Wangsen Cao