| First Author | Baumann L | Year | 2019 |
| Journal | Bone | Volume | 120 |
| Pages | 285-296 | PubMed ID | 30414510 |
| Mgi Jnum | J:271288 | Mgi Id | MGI:6277860 |
| Doi | 10.1016/j.bone.2018.11.003 | Citation | Baumann L, et al. (2019) Deletion of nicotinic acetylcholine receptor alpha9 in mice resulted in altered bone structure. Bone 120:285-296 |
| abstractText | 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 alpha10 was down-regulated in osteogenic differentiated mesenchymal stem cells of patients with osteoporosis whereas the expression of subunit alpha9 was not altered. Since nAChR subunits alpha9 and alpha10 are often combined in a functional receptor, we analyzed here the bone of adult female KO mice with single deletion of either nAChR alpha9 (alpha9KO) or alpha10 (alpha10KO). Biomechanical testing showed a significant decrease of bending stiffness and maximal breaking force in alpha9KO compared to their corresponding wild type mice. Furthermore, an increase in trabecular pattern factor (Tb.Pf) and structure model index (SMI) was detected by muCT in alpha9KO indicating reduced bone mass. On the mRNA level a decrease of Collagen 1alpha1 and Connexin-43 was measured by real-time RT-PCR in alpha9KO 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 alpha9KO compared to their wild type mice, while alpha10KO showed no differences. In conclusion, we demonstrate alterations in bone strength, structure and bio-marker expression in alpha9KO mice which imply the induction of osteocyte degeneration. Thus, our data suggest that nAChR containing the alpha9 subunit might be involved in the homeostasis of osteocytes and therefore in bone mass regulation. |
