Journal article

Publication year: 2019

Pages: 285-296

Journal: Bone

Volume number: 120

ISSN: 8756-3282

eISSN: 1873-2763

Open access status: Hybrid

DOI Link: https://doi.org/10.1016/j.bone.2018.11.003

Publisher: Elsevier

Abstract: 

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 alpha 10 was down-regulated in osteogenic differentiated mesenchymal stem cells of patients with osteoporosis whereas the expression of subunit alpha 9 was not altered. Since nAChR subunits alpha 9 and alpha 10 are often combined in a functional receptor, we analyzed here the bone of adult female KO mice with single deletion of either nAChR alpha9 (alpha 9KO) or alpha10 (alpha 10KO).

Biomechanical testing showed a significant decrease of bending stiffness and maximal breaking force in alpha 9KO compared to their corresponding wild type mice. Furthermore, an increase in trabecular pattern factor (Tb.Pf) and structure model index (SMI) was detected by mu CT in alpha 9KO indicating reduced bone mass. On the mRNA level a decrease of Collagen 1 alpha 1 and Connexin-43 was measured by real-time RT-PCR in alpha 9KO 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 alpha 9KO compared to their wild type mice, while alpha 10KO showed no differences.

In conclusion, we demonstrate alterations in bone strength, structure and bio-marker expression in alpha 9KO mice which imply the induction of osteocyte degeneration. Thus, our data suggest that nAChR containing the alpha 9 subunit might be involved in the homeostasis of osteocytes and therefore in bone mass regulation.

Harvard Citation style: Baumann, L., Kauschke, V., Vikman, A., Dueselen, L., Krasteva-Christ, G., Kampschulte, M., et al. (2019) Deletion of nicotinic acetylcholine receptor alpha9 in mice resulted in altered bone structure, Bone, 120, pp. 285-296. https://doi.org/10.1016/j.bone.2018.11.003

APA Citation style: Baumann, L., Kauschke, V., Vikman, A., Dueselen, L., Krasteva-Christ, G., Kampschulte, M., Heiss, C., Yee, K., Vetter, D., & Lips, K. (2019). Deletion of nicotinic acetylcholine receptor alpha9 in mice resulted in altered bone structure. Bone. 120, 285-296. https://doi.org/10.1016/j.bone.2018.11.003