Role of calcitonin gene-related peptide in functional adaptation of the skeleton.

ABSTRACT: Peptidergic sensory nerve fibers innervating bone and periosteum are rich in calcitonin gene-related peptide (CGRP), an osteoanabolic neurotransmitter. There are two CGRP isoforms, CGRP? and CGRP?. Sensory fibers are a potential means by which the nervous system may detect and respond to loading events within the skeleton. However, the functional role of the nervous system in the response of bone to mechanical loading is unclear. We used the ulna end-loading model to induce an adaptive modeling response in CGRP? and CGRP? knockout mouse lines and their respective wildtype controls. For each knockout mouse line, groups of mice were treated with cyclic loading or sham-loading of the right ulna. A third group of mice received brachial plexus anesthesia (BPA) of the loaded limb before mechanical loading. Fluorochrome labels were administered at the time of loading and 7 days later. Ten days after loading, bone responses were quantified morphometrically. We hypothesized that CGRP signaling is required for normal mechanosensing and associated load-induced bone formation. We found that mechanically-induced activation of periosteal mineralizing surface in mice and associated blocking with BPA were eliminated by knockout of CGRP? signaling. This effect was not evident in CGRP? knockout mice. We also found that mineral apposition responses to mechanical loading and associated BPA blocking were retained with CGRP? deletion. We conclude that activation of periosteal mineralizing surfaces in response to mechanical loading of bone is CGRP?-dependent in vivo. This suggests that release of CGRP from sensory peptidergic fibers in periosteum and bone has a functional role in load-induced bone formation.

SUBMITTER: Sample SJ 

PROVIDER: S-EPMC4275203 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature