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01.12.2015 | Research article | Ausgabe 1/2015 Open Access

BMC Musculoskeletal Disorders 1/2015

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

Zeitschrift:
BMC Musculoskeletal Disorders > Ausgabe 1/2015
Autoren:
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
Wichtige Hinweise

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

Study design: KSL, TB, LD, MKa, OK. Study conduct: KSL, AL, LD, AI, CH, RS, OK. Data collection: ÖY, MKn, IP, VK, MM, AH, PS, YL. Data analysis: KSL, MKn, ÖY, MR, TB, MKa, MR, Data interpretation: KSL, ÖY, MKn, IP, VK, AH, PS, MR, TB, YL, MKa, AI, CH, RS, OK, LD. Drafting manuscript: KSL, ÖY, MKn, VK, IP, AH, PS, MR, TB, YL, MKa, LD. Revising manuscript content: MM, AL, AI, CH, RS, OK. Approving final version of manuscript: KSL, ÖY, MKn, IP, VK, MM, AH, PS, MR, TB, YL, MKa, AL, LD, AI, CH, RS, OK. KSL takes responsibility for the integrity of the data analysis.

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.
Literatur
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