title: Small changes in bone structure of female α7 nicotinic acetylcholine receptor knockout mice.
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.
authors: Laboratory for Experimental Trauma Surgery, Justus-Liebig University Giessen, Kerkraderstr. 9, 35394, Giessen, Germany. Katrin.S.Lips@chiru.med.uni-giessen.de.
authors: Katrin S
authors: KS
authors: Lips
authors: Laboratory for Experimental Trauma Surgery, Justus-Liebig University Giessen, Kerkraderstr. 9, 35394, Giessen, Germany. oetzi282@web.de.
authors: Özcan
authors: Ö
authors: Yanko
authors: Laboratory for Experimental Trauma Surgery, Justus-Liebig University Giessen, Kerkraderstr. 9, 35394, Giessen, Germany. mathias.kneffel@t-online.de.
authors: Mathias
authors: M
authors: Kneffel
authors: Laboratory for Experimental Trauma Surgery, Justus-Liebig University Giessen, Kerkraderstr. 9, 35394, Giessen, Germany. imke.panzer@googlemail.com.
authors: Imke
authors: I
authors: Panzer
authors: Laboratory for Experimental Trauma Surgery, Justus-Liebig University Giessen, Kerkraderstr. 9, 35394, Giessen, Germany. Vivien.Kauschke@chiru.med.uni-giessen.de.
authors: Vivien
authors: V
authors: Kauschke
authors: Laboratory for Experimental Trauma Surgery, Justus-Liebig University Giessen, Kerkraderstr. 9, 35394, Giessen, Germany. maria.madzharova@googlemail.com.
authors: Maria
authors: M
authors: Madzharova
authors: Institute for Physical Chemistry, Justus-Liebig University Giessen, Heinrich-Buff-Ring 58, 35392, Giessen, Germany. Anja.Henss@phys.Chemie.uni-giessen.de.
authors: Anja
authors: A
authors: Henss
authors: Institute for Physical Chemistry, Justus-Liebig University Giessen, Heinrich-Buff-Ring 58, 35392, Giessen, Germany. peter.Schmitz@materialwiss.uni-giessen.de.
authors: Peter
authors: P
authors: Schmitz
authors: Institute for Physical Chemistry, Justus-Liebig University Giessen, Heinrich-Buff-Ring 58, 35392, Giessen, Germany. Marcus.Rohnke@phys.chemie.uni-giessen.de.
authors: Marcus
authors: M
authors: Rohnke
authors: Institute of Radiology, University Medical Center Erlangen, Friedrich-Alexander University Erlangen-Nuernberg, Palmsanlage 5, 91054, Erlangen, Germany. tobias.baeuerle@uk-erlangen.de.
authors: Tobias
authors: T
authors: Bäuerle
authors: Department of Medical Physics in Radiology, German Cancer Research Center, INF 280, D-69120, Heidelberg, Germany. liufrances2000@googlemail.com.
authors: Yifei
authors: Y
authors: Liu
authors: Department of Radiology, Justus-Liebig University Giessen, Schubertstr. 81, 35392, Giessen, Germany. Marian.Kampschulte@radiol.med.uni-giessen.de.
authors: Marian
authors: M
authors: Kampschulte
authors: Department of Diagnostic and Interventional Radiology, BG Trauma Hospital, Friedberger Landstraße 430, 60389, Frankfurt/Main, Germany. AlexanderC.Langheinrich@BGU-Frankfurt.de.
authors: Alexander C
authors: AC
authors: Langheinrich
authors: Institute of Orthopaedic Research and Biomechanics, Center of Musculoskeletal Research University of Ulm, Ulm, Germany. Lutz.duerselen@uni-ulm.de.
authors: Lutz
authors: L
authors: Dürselen
authors: Institute of Orthopaedic Research and Biomechanics, Center of Musculoskeletal Research University of Ulm, Ulm, Germany. anita.ignatius@uni-ulm.de.
authors: Anita
authors: A
authors: Ignatius
authors: Department of Trauma Surgery Giessen, University Hospital of Giessen-Marburg, Justus-Liebig University Giessen, Rudolf-Buchheim-Str. 7, 35392, Giessen, Germany. Christian.Heiss@chiru.med.uni-giessen.de.
authors: Christian
authors: C
authors: Heiss
authors: Laboratory for Experimental Trauma Surgery, Justus-Liebig University Giessen, Kerkraderstr. 9, 35394, Giessen, Germany. Reinhard.Schnettler@chiru.med.uni-giessen.de.|Department of Trauma Surgery Giessen, University Hospital of Giessen-Marburg, Justus-Liebig University Giessen, Rudolf-Buchheim-Str. 7, 35392, Giessen, Germany. Reinhard.Schnettler@chiru.med.uni-giessen.de.
authors: Reinhard
authors: R
authors: Schnettler
authors: Laboratory for Experimental Trauma Surgery, Justus-Liebig University Giessen, Kerkraderstr. 9, 35394, Giessen, Germany. olaf.kilian@gmx.de.|Department of Orthopedics and Trauma, Zentralklinik Bad Berka, Robert-Koch-Allee 9, 99437, Bad Berka, Germany. olaf.kilian@gmx.de.
authors: Olaf
authors: O
authors: Kilian
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density; D001853:Bone Marrow / Q000098:blood supply; D001862:Bone Resorption; D001842:Bone and Bones / Q000033:anatomy & histology* / Q000648:ultrastructure; D005260:Female; D008297:Male; D018345:Mice, Knockout; D008833:Microcirculation; D010012:Osteogenesis / Q000502:physiology*; D012737:Sex Factors; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism*
chemical_list: D064569:alpha7 Nicotinic Acetylcholine Receptor
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