The nicotinic acetylcholine receptor α7 subunit is an essential negative regulator of bone mass

Kazuaki Mito, Yuiko Sato, Tami Kobayashi, Kana Miyamoto, Eriko Nitta, Atsushi Iwama, Morio Matsumoto, Masaya Nakamura, Kazuki Sato, Takeshi Miyamoto

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Article number45597
JournalScientific reports
Volume7
DOIs
Publication statusPublished - 2017 Mar 28

ASJC Scopus subject areas

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