Nrf2 epigenetic derepression induced by running exercise protects against osteoporosis

摘要

Nrf2 is a critical antiosteoporotic factor suppressed in osteoporotic femurs. Representative photomicrographs of (a) H&E-stained (the upper panel, the arrows indicate trabeculae) and micro-CT-scanned (μ-CT, the lower panel) distal femur sections and (b) micro-CT 3D trabecular architecture of distal femurs from the Nrf2 knockout mice (Nfe2l2−/−) and wild-type littermates (WT) that underwent sham treatment or ovariectomy (Ovx) for 5 weeks (6 mice in each group). c Quantitative analysis of the ratio of sectional trabeculae over total area (Trabe/Total), microstructural bone mineral density (BMD, mg·ccm−1), the ratio of bone volume to tissue volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp) of the μ-CT-scanned distal femurs in Fig. 1b. Data are presented as the mean ± SEM. *P < 0.05, two-way ANOVA. d Western blot analysis of Nrf2 and collagen 1 (Col 1) from the femoral homogenates of 3 healthy controls/4 patients with OP, sham/ovariectomized female mice, and young (3 months)/old (25 months) male mice (6 mice in each group, three or two randomly selected samples are shown). β-actin served as the internal control. WB quantifications are shown underneath the blots. Relative values are presented as the mean ± SEM of all human and mouse samples. *P < 0.05, one-way ANOVA. e Representative femur sections of the sham and ovariectomized mice stained for Nrf2 by immunohistochemistry (IHC). The lower panel images are enlarged frames in the upper panel. The positively stained cells in brown are indicated by arrows