The nicotinic acetylcholine receptor α7 subunit is an essential negative regulator of bone mass.
The nicotinic acetylcholine receptor α7 subunit is an essential negative regulator of bone mass.
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DOI：
10.1038/srep45597
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发表时间：
2017-03-28
影响因子：
4.6
通讯作者：
Miyamoto T
中科院分区：
文献类型：
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作者：
Mito K;Sato Y;Kobayashi T;Miyamoto K;Nitta E;Iwama A;Matsumoto M;Nakamura M;Sato K;Miyamoto T
据报道，烟碱受体α 7 nAchR调节脑和心脏组织中的迷走神经靶点。在这里，我们发现nAchR 7 −/−小鼠由于破骨细胞形成减少而表现出骨量增加，伴随着血清中骨保护素/RANKL比值升高。野生型小鼠的迷走神经切断术也显著增加了血清骨保护素/RANKL比值，在nAchR 7 −/−小鼠中观察到的骨量升高在α 7 nAchR/骨保护素双重缺陷小鼠中逆转。α 7 nAchR缺失显著增加Mac 1阳性巨噬细胞中TNFα的表达，TNFα增加成骨细胞中骨保护素/RANKL的比例。在nAchR 7 −/−小鼠中靶向TNFα使血清骨保护素/RANKL比值和骨量正常化。给予野生型小鼠尼古丁（一种α 7 nAchR配体）可增加血清RANKL水平。因此，迷走神经刺激巨噬细胞通过α 7 nAchR调节破骨细胞形成来调节骨量。
The nicotinic receptor α7nAchR reportedly regulates vagal nerve targets in brain and cardiac tissue. Here we show that nAchR7−/− mice exhibit increased bone mass due to decreased osteoclast formation, accompanied by elevated osteoprotegerin/RANKL ratios in serum. Vagotomy in wild-type mice also significantly increased the serum osteoprotegerin/RANKL ratio, and elevated bone mass seen in nAchR7−/− mice was reversed in α7nAchR/osteoprotegerin-doubly-deficient mice. α7nAchR loss significantly increased TNFα expression in Mac1-positive macrophages, and TNFα increased the osteoprotegerin/RANKL ratio in osteoblasts. Targeting TNFα in nAchR7−/− mice normalized both serum osteoprotegerin/RANKL ratios and bone mass. Administration of nicotine, an α7nAchR ligand, to wild-type mice increased serum RANKL levels. Thus, vagal nerve stimulation of macrophages via α7nAchR regulates bone mass by modulating osteoclast formation.