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BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2015

Open Access 01-12-2015 | Research article

Small changes in bone structure of female α7 nicotinic acetylcholine receptor knockout mice

Authors: Katrin S Lips, Özcan Yanko, Mathias Kneffel, Imke Panzer, Vivien Kauschke, Maria Madzharova, Anja Henss, Peter Schmitz, Marcus Rohnke, Tobias Bäuerle, Yifei Liu, Marian Kampschulte, Alexander C Langheinrich, Lutz Dürselen, Anita Ignatius, Christian Heiss, Reinhard Schnettler, Olaf Kilian

Published in: BMC Musculoskeletal Disorders | Issue 1/2015

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Abstract

Background

Recently, analysis of bone from knockout mice identified muscarinic acetylcholine receptor subtype M3 (mAChR M3) and nicotinic acetylcholine receptor (nAChR) subunit α2 as positive regulator of bone mass accrual whereas of male mice deficient for α7-nAChR (α7KO) did not reveal impact in regulation of bone remodeling. Since female sex hormones are involved in fair coordination of osteoblast bone formation and osteoclast bone degradation we assigned the current study to analyze bone strength, composition and microarchitecture of female α7KO compared to their corresponding wild-type mice (α7WT).

Methods

Vertebrae and long bones of female 16-week-old α7KO (n = 10) and α7WT (n = 8) were extracted and analyzed by means of histological, radiological, biomechanical, cell- and molecular methods as well as time of flight secondary ion mass spectrometry (ToF-SIMS) and transmission electron microscopy (TEM).

Results

Bone of female α7KO revealed a significant increase in bending stiffness (p < 0.05) and cortical thickness (p < 0.05) compared to α7WT, whereas gene expression of osteoclast marker cathepsin K was declined. ToF-SIMS analysis detected a decrease in trabecular calcium content and an increase in C4H6N+ (p < 0.05) and C4H8N+ (p < 0.001) collagen fragments whereas a loss of osteoid was found by means of TEM.

Conclusions

Our results on female α7KO bone identified differences in bone strength and composition. In addition, we could demonstrate that α7-nAChRs are involved in regulation of bone remodelling. In contrast to mAChR M3 and nAChR subunit α2 the α7-nAChR favours reduction of bone strength thereby showing similar effects as α7β2-nAChR in male mice. nAChR are able to form heteropentameric receptors containing α- and β-subunits as well as the subunits α7 can be arranged as homopentameric cation channel. The different effects of homopentameric and heteropentameric α7-nAChR on bone need to be analysed in future studies as well as gender effects of cholinergic receptors on bone homeostasis.
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Metadata
Title
Small changes in bone structure of female α7 nicotinic acetylcholine receptor knockout mice
Authors
Katrin S Lips
Özcan Yanko
Mathias Kneffel
Imke Panzer
Vivien Kauschke
Maria Madzharova
Anja Henss
Peter Schmitz
Marcus Rohnke
Tobias Bäuerle
Yifei Liu
Marian Kampschulte
Alexander C Langheinrich
Lutz Dürselen
Anita Ignatius
Christian Heiss
Reinhard Schnettler
Olaf Kilian
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2015
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/s12891-015-0459-8

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