The nicotinic acetylcholine receptor ?7 subunit is an essential negative regulator of bone mass.

ABSTRACT: The nicotinic receptor ?7nAchR 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 ?7nAchR/osteoprotegerin-doubly-deficient mice. ?7nAchR loss significantly increased TNF? expression in Mac1-positive macrophages, and TNF? increased the osteoprotegerin/RANKL ratio in osteoblasts. Targeting TNF? in nAchR7^-/- mice normalized both serum osteoprotegerin/RANKL ratios and bone mass. Administration of nicotine, an ?7nAchR ligand, to wild-type mice increased serum RANKL levels. Thus, vagal nerve stimulation of macrophages via ?7nAchR regulates bone mass by modulating osteoclast formation.

SUBMITTER: Mito K 

PROVIDER: S-EPMC5368561 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature