Low-intensity pulsed ultrasound enhances the positive effects of high-intensity treadmill exercise on bone in rats

Introduction Moderate exercise benefits bone health, but excessive loading leads to bone fatigue and a decline in mechanical properties. Low-intensity pulsed ultrasound (LIPUS) can stimulate bone formation. The purpose of this study was to explore whether LIPUS could augment the skeletal benefits of high-intensity exercise. Materials and methods MC3T3-E1 osteoblasts were treated with LIPUS at 80 mW/cm 2 or 30 mW/cm 2 for 20 min/day. Forty rats were divided into sham treatment normal control (Sham-NC), sham treatment high-intensity exercise (Sham-HIE), 80 mW/cm 2 LIPUS (LIPUS80), and high-intensity exercise combined with 80 mW/cm 2 LIPUS (LIPUS80-HIE). The rats in HIE group were subjected to 30 m/min slope treadmill exercise for 90 min/day, 6 days/week for 12 weeks. The LIPUS80-HIE rats were irradiated with LIPUS (1 MHz, 80 mW/cm 2 ) for 20 min/day at bilateral hind limb after exercise. Results LIPUS significantly accelerated the proliferation, differentiation, mineralization, and migration of MC3T3-E1 cells. Compared to 30 mW/cm 2 LIPUS, 80 mW/cm 2 LIPUS got better promotion effect. 12 weeks of high-intensity exercise significantly reduced the muscle force, which was significantly reversed by LIPUS. Compared with the Sham-NC group, Sham-HIE group significantly optimized bone microstructure and enhanced mechanical properties of femur, and LIPUS80-HIE further enhanced the improvement effect on bone. The mechanisms may be related to activate Wnt/β-catenin signal pathway and then up-regulate the protein expression of Runx2 and VEGF, the key factors of osteogenesis and angiogenesis. Conclusion LIPUS could augment the skeletal benefits of high-intensity exercise through Wnt/β-catenin signal pathway.