Exercise mitigates the stunting effect of cold temperature on limb elongation in mice by increasing solute delivery to the growth plate

Abstract

Ambient temperature and physical activity modulate bone elongation in mammals, but mechanisms underlying this plasticity are not understood. Longitudinal bone growth occurs in cartilaginous plates, which receive nutritional support via transport of solutes from the vasculature. We subjected weanling mice to temperature and wheel activity to test the hypothesis that activity and high temperature promote bone lengthening by increasing solute delivery to growth plates. We show that exercise mitigates the stunting effect of cold temperature on limb elongation after only 11 days of wheel running. Runners all had significantly lengthened limbs regardless of temperature, while non‐runners had shorter limbs that correlated with housing temperature. Tail length was impacted only by temperature, indicating the exercise effect was localized to limb bones and was not a systemic reaction. In vivo multiphoton imaging of systemically‐introduced tracers revealed enhanced solute delivery to tibial growth plates of wheel‐running mice. The temperature effect was minimal, suggesting that solute transport predominates the exercise growth response. These results provide evidence for the role of solute transport in exercised‐augmented limb elongation and are important for understanding limb length variation among mammals in different environments. Supported by NIH‐RO1AR052003‐04 and AAA Postdoctoral Fellowship.