Deletion of nicotinic acetylcholine receptor alpha9 in mice resulted in altered bone structure.
Alkaline Phosphatase
/ metabolism
Animals
Animals, Newborn
Bone and Bones
/ anatomy & histology
Cancellous Bone
/ anatomy & histology
Cortical Bone
/ anatomy & histology
Female
Femur
/ anatomy & histology
Gene Deletion
Mice, Inbred C57BL
Mice, Knockout
Osteoblasts
/ metabolism
Osteoclasts
/ metabolism
Osteocytes
/ metabolism
Receptors, Nicotinic
/ deficiency
Bending stiffness
Collagen 1α1
Connexin-43
Micro-CT
Non-neuronal cholinergic system
nAChR α10
Journal
Bone
ISSN: 1873-2763
Titre abrégé: Bone
Pays: United States
ID NLM: 8504048
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
09
05
2018
revised:
17
10
2018
accepted:
05
11
2018
pubmed:
11
11
2018
medline:
20
2
2020
entrez:
11
11
2018
Statut:
ppublish
Résumé
Alterations in bone strength and structure were found in knockout (KO) mouse strains with deletion of several acetylcholine receptors. Interestingly, the expression of the nicotinic acetylcholine receptors (nAChR) subunit α10 was down-regulated in osteogenic differentiated mesenchymal stem cells of patients with osteoporosis whereas the expression of subunit α9 was not altered. Since nAChR subunits α9 and α10 are often combined in a functional receptor, we analyzed here the bone of adult female KO mice with single deletion of either nAChR alpha9 (α9KO) or alpha10 (α10KO). Biomechanical testing showed a significant decrease of bending stiffness and maximal breaking force in α9KO compared to their corresponding wild type mice. Furthermore, an increase in trabecular pattern factor (Tb.Pf) and structure model index (SMI) was detected by μCT in α9KO indicating reduced bone mass. On the mRNA level a decrease of Collagen 1α1 and Connexin-43 was measured by real-time RT-PCR in α9KO while no alteration of osteoclast markers was detected in either mouse strain. Using electron microcopy we observed an increase in the number of osteocytes that showed signs of degeneration and cell death in the α9KO compared to their wild type mice, while α10KO showed no differences. In conclusion, we demonstrate alterations in bone strength, structure and bio-marker expression in α9KO mice which imply the induction of osteocyte degeneration. Thus, our data suggest that nAChR containing the α9 subunit might be involved in the homeostasis of osteocytes and therefore in bone mass regulation.
Identifiants
pubmed: 30414510
pii: S8756-3282(18)30424-1
doi: 10.1016/j.bone.2018.11.003
pmc: PMC6492625
mid: NIHMS1015597
pii:
doi:
Substances chimiques
Chrna9 protein, mouse
0
Receptors, Nicotinic
0
Alkaline Phosphatase
EC 3.1.3.1
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
285-296Subventions
Organisme : NIGMS NIH HHS
ID : P30 GM103328
Pays : United States
Organisme : NIDCD NIH HHS
ID : R21 DC015124
Pays : United States
Informations de copyright
Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
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