Treadmill running exercise prevents senile osteoporosis and upregulates the Wnt signaling pathway in SAMP6 mice

Abstract

This study examined the effects of different exercise intensities and durations on bone mineral density (BMD) and bone strength in senescence-accelerated mouse prone 6 (SAMP6) and determined the involvement of the Wnt signaling pathway in exercise-induced osteogenesis. Three-month-old male SAMP6 mice were randomly assigned to different speeds of treadmill running exercise representing low, medium and high intensity, with the duration of five and nine weeks, respectively. We showed that medium-intensity exercise had positive effects on skeletal health, including BMD and bone strength, and the efficacy was higher than that of low-intensity exercise. Interestingly, high-intensity exercise can maintain or even increase bone strength, despite its negative effects on bone mass. Nine weeks of exercise was superior to 5 weeks of exercise, particularly for low-intensity exercise. Furthermore, these effects of exercise-induced osteogenesis are accompanied by activation of the Wnt signaling pathway. Taken together, these results suggest that the positive effects of exercise on osteoporosis prevention are intensity and duration-dependent, and may involve the regulation of Wnt signaling pathways.

Keywords: Gerotarget; SAMP6; Wnt signaling pathway; exercise; osteoporosis; senile.

Figure 1. Effects of exercise on body weight and bone mineral density

a., b. Body weight of mice in each group. c. Bone mineral density of mice in each group. Data are represented as mean +/− SD (n = 6). *: P < 0.05. R, SAMR1 non-exercise group; C, SAMP6, non-exercise group; L, SAMP6, low-intensity group; M, SAMP6, medium-intensity group; H1, SAMP6, high-intensity group.

Figure 2. Effects of exercise on bone biomechanics

a. Effects of exercise on bone ultimate force. b. Effects of exercise on bone yield stress. c. Effects of exercise on bone elastic modulus. d. Effects of exercise on cross sectional area. Data are represented as mean +/− SD (n = 6). *: P < 0.05, **: P < 0.01. R, SAMR1 non-exercise group; C, SAMP6, non-exercise group; L, SAMP6, low-intensity group; M, SAMP6, medium-intensity group; H1, SAMP6, high-intensity group.

Figure 3. Changes of Wnt1 mRNA expression in the left tibia

a. Representative images of Wnt1 mRNA expression by in situ hybridization in each group. The positive cells stained by brown color. b. Wnt1 mRNA expression. Percentage of positive cells were calculated from more than five high-power fields (× 400). Data are represented as mean +/− SD (n = 6). *: P < 0.05, **: P < 0.01. c. Location of in situ hybridization. R, SAMR1 non-exercise group; C, SAMP6, non-exercise group; L, SAMP6, low-intensity group; M, SAMP6, medium-intensity group; H1, SAMP6, high-intensity group.

Figure 4. Changes of Lrp5 mRNA expression in the left tibia

a. Representative images of Lrp5 mRNA expression by in situ hybridization in each group. The positive cells stained by brown color. b. Lrp5 mRNA expression. Percentage of positive cells were calculated from more than five high-power fields (× 400). Data are represented as mean +/− SD (n = 6). *: P < 0.05, **: P < 0.01. c. Location of in situ hybridization. R, SAMR1 non-exercise group; C, SAMP6, non-exercise group; L, SAMP6, low-intensity group; M, SAMP6 , medium-intensity group; H1, SAMP6, high-intensity group.

Figure 5. Changes of β-catenin mRNA expression in the left tibia

a. Representative images of β-catenin mRNA expression by in situ hybridization in each group. The positive cells stained by brown color. b. β-catenin mRNA expression. Percentage of positive cells were calculated from more than five high-power fields (× 400). Data are represented as mean +/− SD (n = 6). *: P < 0.05, **: P < 0.01. c. Location of in situ hybridization. R, SAMR1 non-exercise group; C, SAMP6, non-exercise group; L, SAMP6, low-intensity group; M, SAMP6, medium-intensity group; H1, SAMP6, high-intensity group.

Figure 6. Effects of exercise on serum levels of ALP, OCN and PTH in each group

a. The serum levels of ALP. b. The serum levels of OCN. c. The serum levels of PTH. Data are represented as mean +/− SD (n = 6). *: P < 0.05, **: P < 0.01. R, SAMR1 non-exercise group; C, SAMP6, non-exercise group; L, SAMP6, low-intensity group; M, SAMP6, medium-intensity group; H1, SAMP6, high-intensity group.