Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Department of Musculoskeletal Reconstruction and Regeneration Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Sci Rep. 2017 Mar 28;7:45597. doi: 10.1038/srep45597.
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.
报道称，烟碱型乙酰胆碱受体α7nAchR 可调节大脑和心脏组织中的迷走神经靶标。在这里，我们发现 nAchR7 小鼠由于破骨细胞形成减少而表现出骨量增加，同时血清中骨保护素/RANKL 比值升高。在野生型小鼠中进行迷走神经切断术也显著增加了血清骨保护素/RANKL 比值，而在 nAchR7 小鼠中观察到的骨量增加在 α7nAchR/骨保护素双重缺陷型小鼠中被逆转。α7nAchR 的缺失显著增加了 Mac1 阳性巨噬细胞中的 TNFα 表达，而 TNFα 增加了成骨细胞中的骨保护素/RANKL 比值。在 nAchR7 小鼠中靶向 TNFα 可使血清骨保护素/RANKL 比值和骨量正常化。尼古丁是一种 α7nAchR 配体，给予野生型小鼠可增加血清 RANKL 水平。因此，迷走神经通过 α7nAchR 刺激巨噬细胞调节骨量，从而调节破骨细胞的形成。
