Inhibition of CGRP signaling impairs fracture healing in mice.


Journal

Journal of orthopaedic research : official publication of the Orthopaedic Research Society
ISSN: 1554-527X
Titre abrégé: J Orthop Res
Pays: United States
ID NLM: 8404726

Informations de publication

Date de publication:
06 2023
Historique:
revised: 06 09 2022
received: 30 05 2022
accepted: 18 10 2022
pmc-release: 01 06 2024
medline: 8 5 2023
pubmed: 26 10 2022
entrez: 25 10 2022
Statut: ppublish

Résumé

Calcitonin gene-related peptide (CGRP) is a neuropeptide produced by sensory nerves and functions as a pain sensor. It acts by binding to the calcitonin-like receptor (CLR, protein; Calcrl, gene). CGRP inhibition has been recently introduced as therapeutic treatment of migraine-associated pain. Previous studies have shown that CGRP stimulates bone formation. The aim of our study is to determine whether the inhibition of CGRP signaling negatively impacted fracture healing. Using α-smooth muscle actin (αSMA) Cre animals crossed with Ai9 reporter mice, we showed that CGRP-expressing nerves are near αSMA + cells in the periosteum. In vitro experiments revealed that periosteal cells express Calcrl and receptor activity modifying protein 1; and CGRP stimulation increased periosteal cell proliferation. Using a tamoxifen-inducible model αSMACre/CLR

Identifiants

pubmed: 36281531
doi: 10.1002/jor.25474
pmc: PMC10123175
mid: NIHMS1844888
doi:

Substances chimiques

Calcitonin Gene-Related Peptide JHB2QIZ69Z
Calcitonin 9007-12-9
Receptors, Calcitonin Gene-Related Peptide 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1228-1239

Subventions

Organisme : NIAMS NIH HHS
ID : R01 AR055607
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR070813
Pays : United States

Informations de copyright

© 2022 Orthopaedic Research Society. Published by Wiley Periodicals LLC.

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Auteurs

Natalie K Y Wee (NKY)

Department of Reconstructive Sciences, University of Connecticut Health Center, Connecticut, Farmington, USA.
Bone Cell Biology and Disease Unit, St Vincent's Institute of Medical Research, Victoria, Fitzroy, Australia.

Sanja Novak (S)

Department of Reconstructive Sciences, University of Connecticut Health Center, Connecticut, Farmington, USA.

Debolina Ghosh (D)

Department of Reconstructive Sciences, University of Connecticut Health Center, Connecticut, Farmington, USA.

Sierra H Root (SH)

Department of Reconstructive Sciences, University of Connecticut Health Center, Connecticut, Farmington, USA.

Ian M Dickerson (IM)

Department of Neuroscience, University of Rochester Medical Center, New York, Rochester, USA.

Ivo Kalajzic (I)

Department of Reconstructive Sciences, University of Connecticut Health Center, Connecticut, Farmington, USA.

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Classifications MeSH