Whole‐body vibration protects against chronic high‐altitude hypoxic bone loss by regulating the nitric oxide/ <scp>HIF</scp> ‐1α axis in osteoblasts

The hypobaric hypoxia environment found at high altitudes imposes various reversible and irreversible detrimental effects on living organisms. Accumulating evidence suggests that hypobaric hypoxia negatively impacts skeleton health by diminishing bone quality and disrupting bone microarchitecture. However, therapeutic strategies to counteract this bone loss remain limited. This study investigates the impact of whole-body vibration (WBV) stimulation on skeletal health of rats continuously exposed to simulated hypobaric hypoxia environment at an altitude of 4500 m for 6 weeks. We found that WBV stimulation at 30 Hz and 0.3 g significantly improved femoral bone mass, microarchitecture, and biomechanical properties in rats exposed to chronic hypobaric hypoxia. Additionally, in vitro studies demonstrated that WBV enhanced osteogenic potential and activity in primary osteoblasts under hypoxia conditions. It also reduced levels of hypoxia-inducible factor 1α (HIF-1α), a key transcription factor involved in cellular response to hypoxia. Conversely, overexpression of HIF-1α significantly inhibited cellular differentiation and osteogenesis in osteoblasts exposed to WBV stimulation under hypoxic conditions. Furthermore, WBV stimulation led to a significant increase in nitric oxide (NO) concentrations in osteoblasts during hypoxic exposure. In vitro experiments showed that blocking of NO synthesis with L-NAME impeded WBV-stimulated osteogenic activity in hypoxia-exposed osteoblasts. In vivo studies demonstrated that inhibiting NO synthesis similarly abolished the positive impact of WBV on bone microarchitecture and biomechanical properties under hypobaric hypoxia. Collectivity, our findings indicate that WBV protects against hypobaric hypoxia-induced bone loss by regulating the NO/HIF-1α axis in osteoblasts, and reveal its clinical potential as a promising non-invasive approach.