Temperature effects on solute transport: In vivo imaging of the growth plate

Abstract

Determining how the environment modulates bone elongation is central to understanding skeletal variation. Ambient temperature and physical activity can alter limb length, but the mechanisms by which they do so remain elusive. Solute delivery to cartilaginous growth plates could play a key role since nutrient supply is critical to bone elongation. Advances in imaging technology have revolutionized our ability to visualize growth plates in vivo, but quantitative methods are still lacking. We developed standards for measuring solute delivery ‐‐defined by amount and entry rate of intravenous tracers‐‐ in tibial growth plates of 5 week old mice using multiphoton microscopy. Following IACUC protocols, we employed an acute temperature model (N=6/group) to test the hypothesis that solute delivery is increased or decreased by warm (36C) or cool (23C) limb temperature, holding other physiological parameters constant. Solute delivery differed as predicted with significantly more tracer in growth plates at 36C. These data validate the sensitivity of the method, which we are now using to assess chronic temperature and exercise effects on limb length and nutrient supply to the growth plate. These results are relevant to strategies for delivering therapeutic agents to growth plates of children and have the potential to greatly advance our understanding of skeletal variability in mammals. Supported by NIH‐RO1AR052003‐04.Grant Funding SourceNIH‐RO1AR052003‐04