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Role of calcitonin gene-related peptide in bone repair after cyclic fatigue loading.

Sample SJ, Hao Z, Wilson AP, Muir P - PLoS ONE (2011)

Bottom Line: Administration of CGRP(8-37) was associated with increased targeted remodeling in the fatigue-loaded ulna.Plasma concentration of TRAP5b was not significantly influenced by either CGRP or CGRP(8-37) administration.CGRP signaling modulates targeted remodeling of microdamage and reparative new bone formation after bone fatigue, and may be part of a neuronal signaling pathway which has regulatory effects on load-induced repair responses within the skeleton.

View Article: PubMed Central - PubMed

Affiliation: Comparative Orthopaedic Research Laboratory, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.

ABSTRACT

Background: Calcitonin gene related peptide (CGRP) is a neuropeptide that is abundant in the sensory neurons which innervate bone. The effects of CGRP on isolated bone cells have been widely studied, and CGRP is currently considered to be an osteoanabolic peptide that has effects on both osteoclasts and osteoblasts. However, relatively little is known about the physiological role of CGRP in-vivo in the skeletal responses to bone loading, particularly fatigue loading.

Methodology/principal findings: We used the rat ulna end-loading model to induce fatigue damage in the ulna unilaterally during cyclic loading. We postulated that CGRP would influence skeletal responses to cyclic fatigue loading. Rats were fatigue loaded and groups of rats were infused systemically with 0.9% saline, CGRP, or the receptor antagonist, CGRP(8-37), for a 10 day study period. Ten days after fatigue loading, bone and serum CGRP concentrations, serum tartrate-resistant acid phosphatase 5b (TRAP5b) concentrations, and fatigue-induced skeletal responses were quantified. We found that cyclic fatigue loading led to increased CGRP concentrations in both loaded and contralateral ulnae. Administration of CGRP(8-37) was associated with increased targeted remodeling in the fatigue-loaded ulna. Administration of CGRP or CGRP(8-37) both increased reparative bone formation over the study period. Plasma concentration of TRAP5b was not significantly influenced by either CGRP or CGRP(8-37) administration.

Conclusions: CGRP signaling modulates targeted remodeling of microdamage and reparative new bone formation after bone fatigue, and may be part of a neuronal signaling pathway which has regulatory effects on load-induced repair responses within the skeleton.

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Related in: MedlinePlus

Bone CGRP is increased by mechanical loading.Cyclic fatigue loading of the right ulna resulted in increased CGRP concentrations in both the fatigue-loaded (right) ulna and the contralateral (left) ulna, when compared to the Baseline group. No differences in CGRP concentrations were seen between the Sham group and the Baseline group. The Fatigue group also had increased CGRP concentrations compared to the Sham group. * −p<0.05 versus the relevant baseline control bone. Error bars represent standard error of the mean. Baseline group n = 12; Sham group n = 12; Fatigue group n = 12.
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pone-0020386-g003: Bone CGRP is increased by mechanical loading.Cyclic fatigue loading of the right ulna resulted in increased CGRP concentrations in both the fatigue-loaded (right) ulna and the contralateral (left) ulna, when compared to the Baseline group. No differences in CGRP concentrations were seen between the Sham group and the Baseline group. The Fatigue group also had increased CGRP concentrations compared to the Sham group. * −p<0.05 versus the relevant baseline control bone. Error bars represent standard error of the mean. Baseline group n = 12; Sham group n = 12; Fatigue group n = 12.

Mentions: To determine the effects of cyclic fatigue loading on bone CGRP concentrations, we quantified CGRP in both the loaded and contralateral ulnae of fatigue-loaded and control rats. The concentration of CGRP was increased in both the loaded right ulna (p<0.05) and the contralateral left ulna (p<0.05) of rats in the Fatigue group, when compared to the Baseline group (Fig. 3). No differences were seen between the Baseline group and the Sham group (p = 0.95). Additionally, no differences in humeral CGRP concentrations were seen between groups.


Role of calcitonin gene-related peptide in bone repair after cyclic fatigue loading.

Sample SJ, Hao Z, Wilson AP, Muir P - PLoS ONE (2011)

Bone CGRP is increased by mechanical loading.Cyclic fatigue loading of the right ulna resulted in increased CGRP concentrations in both the fatigue-loaded (right) ulna and the contralateral (left) ulna, when compared to the Baseline group. No differences in CGRP concentrations were seen between the Sham group and the Baseline group. The Fatigue group also had increased CGRP concentrations compared to the Sham group. * −p<0.05 versus the relevant baseline control bone. Error bars represent standard error of the mean. Baseline group n = 12; Sham group n = 12; Fatigue group n = 12.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3111413&req=5

pone-0020386-g003: Bone CGRP is increased by mechanical loading.Cyclic fatigue loading of the right ulna resulted in increased CGRP concentrations in both the fatigue-loaded (right) ulna and the contralateral (left) ulna, when compared to the Baseline group. No differences in CGRP concentrations were seen between the Sham group and the Baseline group. The Fatigue group also had increased CGRP concentrations compared to the Sham group. * −p<0.05 versus the relevant baseline control bone. Error bars represent standard error of the mean. Baseline group n = 12; Sham group n = 12; Fatigue group n = 12.
Mentions: To determine the effects of cyclic fatigue loading on bone CGRP concentrations, we quantified CGRP in both the loaded and contralateral ulnae of fatigue-loaded and control rats. The concentration of CGRP was increased in both the loaded right ulna (p<0.05) and the contralateral left ulna (p<0.05) of rats in the Fatigue group, when compared to the Baseline group (Fig. 3). No differences were seen between the Baseline group and the Sham group (p = 0.95). Additionally, no differences in humeral CGRP concentrations were seen between groups.

Bottom Line: Administration of CGRP(8-37) was associated with increased targeted remodeling in the fatigue-loaded ulna.Plasma concentration of TRAP5b was not significantly influenced by either CGRP or CGRP(8-37) administration.CGRP signaling modulates targeted remodeling of microdamage and reparative new bone formation after bone fatigue, and may be part of a neuronal signaling pathway which has regulatory effects on load-induced repair responses within the skeleton.

View Article: PubMed Central - PubMed

Affiliation: Comparative Orthopaedic Research Laboratory, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.

ABSTRACT

Background: Calcitonin gene related peptide (CGRP) is a neuropeptide that is abundant in the sensory neurons which innervate bone. The effects of CGRP on isolated bone cells have been widely studied, and CGRP is currently considered to be an osteoanabolic peptide that has effects on both osteoclasts and osteoblasts. However, relatively little is known about the physiological role of CGRP in-vivo in the skeletal responses to bone loading, particularly fatigue loading.

Methodology/principal findings: We used the rat ulna end-loading model to induce fatigue damage in the ulna unilaterally during cyclic loading. We postulated that CGRP would influence skeletal responses to cyclic fatigue loading. Rats were fatigue loaded and groups of rats were infused systemically with 0.9% saline, CGRP, or the receptor antagonist, CGRP(8-37), for a 10 day study period. Ten days after fatigue loading, bone and serum CGRP concentrations, serum tartrate-resistant acid phosphatase 5b (TRAP5b) concentrations, and fatigue-induced skeletal responses were quantified. We found that cyclic fatigue loading led to increased CGRP concentrations in both loaded and contralateral ulnae. Administration of CGRP(8-37) was associated with increased targeted remodeling in the fatigue-loaded ulna. Administration of CGRP or CGRP(8-37) both increased reparative bone formation over the study period. Plasma concentration of TRAP5b was not significantly influenced by either CGRP or CGRP(8-37) administration.

Conclusions: CGRP signaling modulates targeted remodeling of microdamage and reparative new bone formation after bone fatigue, and may be part of a neuronal signaling pathway which has regulatory effects on load-induced repair responses within the skeleton.

Show MeSH
Related in: MedlinePlus