Open AccessThe nicotinic acetylcholine receptor α7 subunit is an essential negative regulator of bone mass
Author(s) -
Kazuyuki Mito,
Yuiko Sato,
Tami Kobayashi,
Kana Miyamoto,
Eriko Nitta,
Atsushi Iwama,
Morio Matsumoto,
Masaya Nakamura,
Kazuki Sato,
Takeshi Miyamoto
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep45597
Subject(s) - osteoprotegerin , rankl , endocrinology , medicine , osteoclast , chemistry , bone remodeling , receptor , bone resorption , tumor necrosis factor alpha , nicotinic acetylcholine receptor , nicotinic agonist , activator (genetics)
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.