Journalartikel

Jahr der Veröffentlichung: 2015

Zeitschrift: BMC Musculoskeletal Disorders

Bandnummer: 16

ISSN: 1471-2474

Open Access Status: Gold

DOI Link: https://doi.org/10.1186/s12891-015-0459-8

Verlag: BioMed Central

Abstract: 

Background: Recently, analysis of bone from knockout mice identified muscarinic acetylcholine receptor subtype M3 (mAChR M3) and nicotinic acetylcholine receptor (nAChR) subunit alpha 2 as positive regulator of bone mass accrual whereas of male mice deficient for alpha 7-nAChR (alpha 7KO) 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 alpha 7KO compared to their corresponding wild-type mice (alpha 7WT).

Methods: Vertebrae and long bones of female 16-week-old alpha 7KO (n = 10) and alpha 7WT (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 alpha 7KO revealed a significant increase in bending stiffness (p < 0.05) and cortical thickness (p < 0.05) compared to alpha 7WT, 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 alpha 7KO bone identified differences in bone strength and composition. In addition, we could demonstrate that alpha 7-nAChRs are involved in regulation of bone remodelling. In contrast to mAChR M3 and nAChR subunit alpha 2 the alpha 7-nAChR favours reduction of bone strength thereby showing similar effects as alpha 7 beta 2-nAChR in male mice. nAChR are able to form heteropentameric receptors containing alpha- and beta-subunits as well as the subunits alpha 7 can be arranged as homopentameric cation channel. The different effects of homopentameric and heteropentameric alpha 7-nAChR on bone need to be analysed in future studies as well as gender effects of cholinergic receptors on bone homeostasis.

Harvard-Zitierstil: Lips, K., Yanko, O., Kneffel, M., Panzer, I., Kauschke, V., Madzharova, M., et al. (2015) Small changes in bone structure of female α7 nicotinic acetylcholine receptor knockout mice, BMC Musculoskeletal Disorders, 16, Article 5. https://doi.org/10.1186/s12891-015-0459-8

APA-Zitierstil: Lips, K., Yanko, O., Kneffel, M., Panzer, I., Kauschke, V., Madzharova, M., Henss, A., Schmitz, P., Rohnke, M., Bauerle, T., Liu, Y., Kampschulte, M., Langheinrich, A., Durselen, L., Ignatius, A., Heiss, C., Schnettler, R., & Kilian, O. (2015). Small changes in bone structure of female α7 nicotinic acetylcholine receptor knockout mice. BMC Musculoskeletal Disorders. 16, Article 5. https://doi.org/10.1186/s12891-015-0459-8