| First Author | Sample SJ | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 12 | Pages | e113959 |
| PubMed ID | 25536054 | Mgi Jnum | J:225387 |
| Mgi Id | MGI:5693209 | Doi | 10.1371/journal.pone.0113959 |
| Citation | Sample SJ, et al. (2014) Role of calcitonin gene-related peptide in functional adaptation of the skeleton. PLoS One 9(12):e113959 |
| abstractText | Peptidergic sensory nerve fibers innervating bone and periosteum are rich in calcitonin gene-related peptide (CGRP), an osteoanabolic neurotransmitter. There are two CGRP isoforms, CGRPalpha and CGRPbeta. 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 CGRPalpha and CGRPbeta 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 CGRPalpha signaling. This effect was not evident in CGRPbeta knockout mice. We also found that mineral apposition responses to mechanical loading and associated BPA blocking were retained with CGRPalpha deletion. We conclude that activation of periosteal mineralizing surfaces in response to mechanical loading of bone is CGRPalpha-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. |
