Morphological and histological adaptation of muscle and bone to loading induced by repetitive activation of muscle

Abstract

Muscular contraction plays a pivotal role in the mechanical environment of bone, but controlledmuscular contractions are rarely used to study the response of bone tomechanical stimuli.Here,we useimplantable stimulators to elicit programmed contractions of the rat tibialis anterior (TA) muscle. Miniature stimulators were implanted in Wistar rats (n = 9) to induce contraction of the left TAevery 30 s for 28 days. The right limbwas used as a contralateral control. Hindlimbs were imaged using microCT. Image data were used for bone measurements, and to construct a finite-element (FE) model simulation of TA forces propagating through the bone. This simulation was used to target subsequent bone histology and measurement of micromechanical properties to areas of high strain. FE mapping of simulated strains revealed peak values in the anterodistal region of the tibia (640 με+30.4 με).This region showed significant increases in cross-sectional area (28.61%, p < 0.05) and bone volume (30.29%, p < 0.05) in the stimulated limb. Histology revealed a large region of new bone, containing clusters of chondrocytes, indicative of endochondral ossification. The new bone region had a lower elastic modulus (8.8+2.2 GPa) when compared with established bone (20+1.4 GPa). Our study provides compelling new evidence of the interplay between muscle and bone. © 2014 The Author(s) Published by the Royal Society. All rights reserved.