Nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) is a transcription factor that is crucial in maintaining cellular redox homeostasis. In female mice, Nrf2 deficiency has been shown to increase bone resorption in the femur. In contrast, treadmill exercise training has been shown to increase bone density in the femur of aged rats. We tested the hypothesis that the absence of Nrf2 would reduce or negate increases in bone density induced by exercise training. We exercise trained male and female wild type Sprague‐Dawley (WT) rats, and their littermates lacking the Nrf2 gene (Nrf2KO). Rats were either exercise trained (EX) on a motor‐driven treadmill 5 days/wk or remained sedentary (SED) in their cages for 10–12 weeks. A mixed moderate aerobic and high‐intensity interval training protocol was utilized. At the end of the training period, femurs were cleaned, then scanned and analyzed using a Scanco Medical uCT35 micro‐CT with a resolution of 12 micron‐voxels. Total volume, bone volume, bone volume/total volume (BV/TV), connectivity and number of trabeculae were evaluated in trabecular bone. In both WT and Nrf2KO male rats, exercise training increased trabecular number (EX: 2.8 ± 0.1 vs. SED: 2.4 ± 0.1; P<0.05) and BV/TV (EX: 0.17± 0.01 vs. SED: 0.13 ± 0.01; P=0.06), and tended to increase connectivity (EX: 31.9 ± 2.5 vs. SED: 24.7 ± 2.5; P=0.09). Surprisingly, total volume, bone volume, BV/TV, connectivity and number of trabeculae were all more than 100% higher in femurs from females as compared to males (female vs. male; P<0.0000001 for all parameters). There were no significant effects of training or Nrf2KO genotype on bone parameters in females. These data suggest that female hormones are powerful regulators of bone growth and remodeling, masking the effects of either deletion of the Nrf2 gene or treadmill exercise.Support or Funding InformationNIH Grant Number R15AG055029This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The magnitude of bone formation and remodeling is linked to both the magnitude of strain placed on the bone and the perfusion of bone. We have previously reported an increase in bone perfusion and bone density that occurs in the femur of old rats with moderate aerobic exercise training. The purpose of this study was to determine the acute and chronic effects of static muscle stretching on bone blood flow and to determine whether chronic stretching affects bone remodeling. Old male Fischer 344 rats were randomized to either a naïve or stretch‐trained group. Static stretching of ankle flexor muscles was achieved by placement of a dorsflexion splint on the left ankle for 30 min/day, 5d/wk for 4wks. The right hindlimb served as a contralateral control (unstretched) limb. Bone blood flow was assessed during and after an acute bout of stretching in naïve rats, and at rest and during exercise in stretch‐trained rats. Following 4 weeks of daily muscle stretching, micro‐CT analysis was used to determine the volume and density of bone and the bone vasculature in the tibia. In naïve rats, placement of the splint increased blood flow to the proximal tibial metaphasis. After 4 weeks of daily stretching, blood flow to the proximal tibial metaphysis was higher in the chronically stretched limb during exercise. Chronic stretching also increased tibial bone weight, and increased total bone volume in both the proximal and distal tibial metaphyses. In trabecular bone immediately below the proximal tibial growth plate, the total volume of bone was increased, but the bone density was not changed. Total intravascular volume also increased in the region of the bone below the growth plate. These data suggest that static muscle stretching increases loading of bone and bone blood flow, leading to bone remodeling and growth which is matched by an increase in bone intravascular volume.Support or Funding InformationNIH R15AG055029This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.