title: Role of calcitonin gene-related peptide in bone repair after cyclic fatigue loading.
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.
  
  
  RESULTS
  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.
authors.affiliation: Comparative Orthopaedic Research Laboratory, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Susannah J
authors.initials: SJ
authors.lastname: Sample
authors.forename: Zhengling
authors.initials: Z
authors.lastname: Hao
authors.forename: Aliya P
authors.initials: AP
authors.lastname: Wilson
authors.forename: Peter
authors.initials: P
authors.lastname: Muir
mesh_terms: D000135:Acid Phosphatase / Q000097:blood; D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D005452:Fluoresceins / Q000378:metabolism; D007527:Isoenzymes / Q000097:blood; D008297:Male; D010012:Osteogenesis / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D000071681:Tartrate-Resistant Acid Phosphatase; D014457:Ulna / Q000378:metabolism* / Q000502:physiology*; D016474:Weight-Bearing; D014945:Wound Healing / Q000187:drug effects
chemical_list: D005452:Fluoresceins; D007527:Isoenzymes; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D015740:Calcitonin Gene-Related Peptide; C007740:fluorexon