role of calcitonin gene-related peptide in bone repair after cyclic fatigue loading在骨修复作用,降钙素相关基因肽循环疲劳载荷.pdfVIP

Role of Calcitonin Gene-Related Peptide in Bone Repair after Cyclic Fatigue Loading Susannah J. Sample, Zhengling Hao, Aliya P. Wilson, Peter Muir* 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, CGRP8–37, 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 CGRP8–37 was associated with increased targeted remodeling in the fatigue-loaded ulna. Administration of CGRP or CGRP8–37 both increased reparative bone formation over the study period. Plasma concentration of TRAP5b was not significantly influenced by either CGRP or CGRP8–37 administration. Conclusions: CGRP signaling modulates targeted remodeling of microdamage and reparative