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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

Remodeling of fatigue loaded bone was increased with administration of CGRP8–37.Treatment with either saline, CGRP or CGRP8–37 for 10 days after cyclic fatigue loading of the right ulna did not affect crack surface density (Cr.S.Dn), but resulted in altered resorption space density (Rs.Sp.Dn). (A) Cr.S.Dn was similar between groups. (B) Rs.Sp.Dn in the right ulna was increased in the CGRP8–37 group compared to the CGRP group and the Saline group. In the left ulna, resorption space number density was increased in the CGRP group, compared to the Saline group and the CGRP8–37 group. ** −p<0.01; *** −p<0.001; versus the relevant saline control bone. Error bars represent range. Saline group n = 8; CGRP group n = 12; CGRP8–37 group n = 12.
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pone-0020386-g005: Remodeling of fatigue loaded bone was increased with administration of CGRP8–37.Treatment with either saline, CGRP or CGRP8–37 for 10 days after cyclic fatigue loading of the right ulna did not affect crack surface density (Cr.S.Dn), but resulted in altered resorption space density (Rs.Sp.Dn). (A) Cr.S.Dn was similar between groups. (B) Rs.Sp.Dn in the right ulna was increased in the CGRP8–37 group compared to the CGRP group and the Saline group. In the left ulna, resorption space number density was increased in the CGRP group, compared to the Saline group and the CGRP8–37 group. ** −p<0.01; *** −p<0.001; versus the relevant saline control bone. Error bars represent range. Saline group n = 8; CGRP group n = 12; CGRP8–37 group n = 12.

Mentions: To quantify fatigue damage and associated osteoclast activation in rats treated with CGRP or CGRP8–37, we measured Cr.S.Dn and Rs.Sp.Dn in both fatigue-loaded right ulnae and the contralateral left ulnae (Fig. 4). No differences in Cr.S.Dn were seen between groups (Fig. 5A). Rats in the CGRP8–37 group had increased Rs.Sp.Dn in their right ulna 10 days after fatigue loading, compared to the CGRP group (p<0.001), and the Saline group (p<0.01) (Fig. 5B). In the contralateral left ulna, Rs.Sp.Dn was increased to a small extent in the CGRP group, compared to both the Saline group (p<0.001) and CGRP8–37 group (p<0.001).


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

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

Remodeling of fatigue loaded bone was increased with administration of CGRP8–37.Treatment with either saline, CGRP or CGRP8–37 for 10 days after cyclic fatigue loading of the right ulna did not affect crack surface density (Cr.S.Dn), but resulted in altered resorption space density (Rs.Sp.Dn). (A) Cr.S.Dn was similar between groups. (B) Rs.Sp.Dn in the right ulna was increased in the CGRP8–37 group compared to the CGRP group and the Saline group. In the left ulna, resorption space number density was increased in the CGRP group, compared to the Saline group and the CGRP8–37 group. ** −p<0.01; *** −p<0.001; versus the relevant saline control bone. Error bars represent range. Saline group n = 8; CGRP group n = 12; CGRP8–37 group n = 12.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3111413&req=5

pone-0020386-g005: Remodeling of fatigue loaded bone was increased with administration of CGRP8–37.Treatment with either saline, CGRP or CGRP8–37 for 10 days after cyclic fatigue loading of the right ulna did not affect crack surface density (Cr.S.Dn), but resulted in altered resorption space density (Rs.Sp.Dn). (A) Cr.S.Dn was similar between groups. (B) Rs.Sp.Dn in the right ulna was increased in the CGRP8–37 group compared to the CGRP group and the Saline group. In the left ulna, resorption space number density was increased in the CGRP group, compared to the Saline group and the CGRP8–37 group. ** −p<0.01; *** −p<0.001; versus the relevant saline control bone. Error bars represent range. Saline group n = 8; CGRP group n = 12; CGRP8–37 group n = 12.
Mentions: To quantify fatigue damage and associated osteoclast activation in rats treated with CGRP or CGRP8–37, we measured Cr.S.Dn and Rs.Sp.Dn in both fatigue-loaded right ulnae and the contralateral left ulnae (Fig. 4). No differences in Cr.S.Dn were seen between groups (Fig. 5A). Rats in the CGRP8–37 group had increased Rs.Sp.Dn in their right ulna 10 days after fatigue loading, compared to the CGRP group (p<0.001), and the Saline group (p<0.01) (Fig. 5B). In the contralateral left ulna, Rs.Sp.Dn was increased to a small extent in the CGRP group, compared to both the Saline group (p<0.001) and CGRP8–37 group (p<0.001).

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