Skeletal response to Yoda1 and whole-body vibration in mice varied with animal age, bone compartment, treatment duration, and radiation exposure.

Abstract

In this study, we investigated the skeletal effects of Yoda1, an agonist of the mechanosensitive Piezo1 channels, and whole-body vibration (WBV), alone and combined, in young mice (8-week-old) and in mature (31- to 36-week-old) mice after radiation exposure. Our goal was to determine whether the two mechanobiology-based interventions, known to induce anabolic response individually in young subjects, could promote bone health of older subjects undergoing cancer treatments such as radiotherapy. Our hypothesis was that the combination of Yoda1 and WBV could improve young skeletons and protect mature skeletons after radiotherapy better than Yoda1 or WBV alone. Our in vivo experiments demonstrated (1) that Yoda1 (5 mg/kg body weight) alone or combined with WBV (0.3 g, 13 Hz, 30 min/day, 5 days/week, 4 weeks) enhanced bone growth similarly (∼2 folds relative to nontreated controls) in young mice; (2) that mature mice were unresponsive to individual interventions but exhibited less polar moment of inertia loss (-56 %) in the tibiae receiving the combination of Yoda1 and WBV (15 min/day) but no radiation exposure; and (3) that the contralateral tibiae receiving fractionated radiation (2 × 8 Gy over three days) did not show different treatment responses in Week 4, while they responded to the combination therapy (increased cortical bone formation) in Week 2. Interestingly, pair comparisons of the irradiated and non-irradiated tibiae of the same animals revealed that radiation exposure resulted in decreased trabecular bone loss regardless of the treatments and increased the percentage of tibiae maintaining better cortical polar moment of inertia and cortical area in the groups receiving Yoda1 or the combination therapy. The complex skeletal responses to Yoda1 and/or WBV were compartment specific (cortical or trabecular bone) and dependent on animal age, radiation exposure, and treatment duration. This study partially supported our original hypothesis, while suggesting the need of finetuning the Yoda1 and WBV regimens and elucidating the underlying mechanisms in order to effectively treat age and radiation induced bone loss.