Validation of a unilateral heating model to increase hindlimb length in growing mice (342.4)

Abstract

Limb length inequality is prevalent in nearly 90% of the population. Differences of 20mm can cause gait asymmetry and chronic back pain. Surgical treatments are invasive and alternatives are needed. Exposure to warm ambient temperature accelerates limb elongation in mice, suggesting that targeted heat could be a noninvasive way to promote limb length equalization. We tested the hypothesis that daily heat exposure on one side of the body will unilaterally increase limb length. Female mice (N=6) were treated with 40C unilateral heat for 40 minutes per day for 14 days post‐weaning. Controls (N=6) were not treated. Femur length was increased 1.3% on the heat‐treated side. Tibial elongation rate, measured by oxytetracycline labeling, was increased >12%. Body mass was unaffected. Histological analysis revealed morphological differences in the growth plate. To validate a protein assay for the next step, we developed western blotting methods to asses IGF‐I activation in whole proximal tibias. We show that IGF‐I (100ng/ml) stimulates Akt phosphorylation after 90 minutes in culture, suggesting that this method will be effective for measuring IGF‐I signaling in heat‐treated bones. This model will be important for elucidating mechanisms of heat‐enhanced growth. Our findings are relevant for the development of non‐invasive heat‐based therapies to increase length of specific bones without surgery.Grant Funding Source: Supported by NASA WV Space Grant Consortium and UK CCTS (NIH UL1TR000117)