Deletion of nicotinic acetylcholine receptor alpha9 in mice resulted in altered bone structure.
Deletion of nicotinic acetylcholine receptor alpha9 in mice resulted in altered bone structure.
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小鼠中烟碱乙酰胆碱受体α9的缺失导致骨结构改变。
DOI：
10.1016/j.bone.2018.11.003
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发表时间：
2019-03
期刊：
影响因子：
4.1
通讯作者：
Lips KS
中科院分区：
文献类型：
--
作者：
Baumann L;Kauschke V;Vikman A;Dürselen L;Krasteva-Christ G;Kampschulte M;Heiss C;Yee KT;Vetter DE;Lips KS
在敲除（KO）小鼠品系中发现了骨强度和结构的改变，其中缺失了几种乙酰胆碱受体。有趣的是，在骨质疏松患者的成骨分化间充质干细胞中，烟碱乙酰胆碱受体（nAChR）亚基α10的表达下调，而亚基α9的表达没有改变。由于nAChR亚基α9和α10通常结合在一个功能性受体中，我们在此分析了nAChR α 9（α 9 KO）或α 10（α 10 KO）单一缺失的成年雌性KO小鼠的骨。生物力学测试显示，与相应的野生型小鼠相比，α 9 KO的弯曲刚度和最大断裂力显著降低。此外，μCT检测到α 9 KO的骨小梁模式因子（Tb.Pf）和结构模型指数（SMI）增加，表明骨量减少。在mRNA水平上，通过实时RT-PCR测量α 9 KO中胶原蛋白1 α 1和连接蛋白-43的减少，而在两种小鼠品系中均未检测到破骨细胞标志物的改变。使用电子显微镜，我们观察到与野生型小鼠相比，α 9 KO小鼠中显示变性和细胞死亡迹象的骨细胞数量增加，而α 10 KO小鼠无差异。总之，我们证明了α 9 KO小鼠骨强度、结构和生物标志物表达的改变，这意味着诱导骨细胞变性。因此，我们的数据表明，含有α9亚基的nAChR可能参与骨细胞的稳态，因此在骨量调节。
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 α10 was down-regulated in osteogenic differentiated mesenchymal stem cells of patients with osteoporosis whereas the expression of subunit α9 was not altered. Since nAChR subunits α9 and α10 are often combined in a functional receptor, we analyzed here the bone of adult female KO mice with single deletion of either nAChR alpha9 (α9KO) or alpha10 (α10KO). Biomechanical testing showed a significant decrease of bending stiffness and maximal breaking force in α9KO compared to their corresponding wild type mice. Furthermore, an increase in trabecular pattern factor (Tb.Pf) and structure model index (SMI) was detected by μCT in α9KO indicating reduced bone mass. On the mRNA level a decrease of Collagen lαl and Connexin-43 was measured by real-time RT-PCR in α9KO 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 α9KO compared to their wild type mice, while α10KO showed no differences. In conclusion, we demonstrate alterations in bone strength, structure and bio-marker expression in α9KO mice which imply the induction of osteocyte degeneration. Thus, our data suggest that nAChR containing the α9 subunit might be involved in the homeostasis of osteocytes and therefore in bone mass regulation.
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影响因子：
2.4
作者：
Cardoso L;Fritton SP;Gailani G;Benalla M;Cowin SC
通讯作者：
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影响因子：
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作者：
Lips, KS;Brüggmann, D;Kummer, W
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作者：
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作者：
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