Bone Injury and Repair Trigger Central and Peripheral NPY Neuronal Pathways.

Cecília J Alves,Daniela M Sousa,Meriem Lamghari,Estrela Neto,Teresa Summavielle,João Ribas,Daniel M Vasconcelos,Inês S Alencastre,Sofia Ferreira,Luc Malaval

doi:10.1371/journal.pone.0165465

Abstract

Bone repair is a specialized type of wound repair controlled by complex multi-factorial events. The nervous system is recognized as one of the key regulators of bone mass, thereby suggesting a role for neuronal pathways in bone homeostasis. However, in the context of bone injury and repair, little is known on the interplay between the nervous system and bone. Here, we addressed the neuropeptide Y (NPY) neuronal arm during the initial stages of bone repair encompassing the inflammatory response and ossification phases in femoral-defect mouse model. Spatial and temporal analysis of transcriptional and protein levels of NPY and its receptors, Y1R and Y2R, reported to be involved in bone homeostasis, was performed in bone, dorsal root ganglia (DRG) and hypothalamus after femoral injury. The results showed that NPY system activity is increased in a time- and space-dependent manner during bone repair. Y1R expression was trigged in both bone and DRG throughout the inflammatory phase, while a Y2R response was restricted to the hypothalamus and at a later stage, during the ossification step. Our results provide new insights into the involvement of NPY neuronal pathways in bone repair.

Highlights

Neuropeptide Y (NPY) is a 36 amino-acid peptide widely distributed in the central and peripheral nervous system, which has been shown to contribute to a broad range of physiological processes including control of feeding behaviour, energy homeostasis, vascular and immune function, pain and stress copping [1,2,3]
The present study shows that the central and peripheral NPY pathways are targeted during the initial stages of bone repair, pointing to an increase in the NPY system activity in response to bone injury
The results suggest a putative role for NPY on the biological events occurring early in bone repair

Summary

Introduction

Neuropeptide Y (NPY) is a 36 amino-acid peptide widely distributed in the central and peripheral nervous system, which has been shown to contribute to a broad range of physiological processes including control of feeding behaviour, energy homeostasis, vascular and immune function, pain and stress copping [1,2,3]. NPY was identified as a powerful regulator of bone mass through both central- and peripheral-mediated pathways [4, 5]. Of the five known NPY receptors (Y1R, Y2R, Y4R, Y5R and Y6R), Y1R and Y2R were reported to be involved in bone homeostasis [4,5,6]. The induced overexpression of hypothalamic NPY in NPY-deficient mice resulted in a significant reduction in bone mass [7] and, in the same line, PLOS ONE | DOI:10.1371/journal.pone.0165465 November 1, 2016

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Conclusion