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- Title
The nicotinic acetylcholine receptor α7 subunit is an essential negative regulator of bone mass.
- Authors
Mito, Kazuaki; Sato, Yuiko; Kobayashi, Tami; Miyamoto, Kana; Nitta, Eriko; Iwama, Atsushi; Matsumoto, Morio; Nakamura, Masaya; Sato, Kazuki; Miyamoto, Takeshi
- Abstract
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.
- Publication
Scientific Reports, 2017, p45597
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/srep45597