First Author | Mito K | Year | 2017 |
Journal | Sci Rep | Volume | 7 |
Pages | 45597 | PubMed ID | 28349965 |
Mgi Jnum | J:275298 | Mgi Id | MGI:6296444 |
Doi | 10.1038/srep45597 | Citation | Mito K, et al. (2017) The nicotinic acetylcholine receptor alpha7 subunit is an essential negative regulator of bone mass. Sci Rep 7:45597 |
abstractText | The nicotinic receptor alpha7nAchR 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 alpha7nAchR/osteoprotegerin-doubly-deficient mice. alpha7nAchR loss significantly increased TNFalpha expression in Mac1-positive macrophages, and TNFalpha increased the osteoprotegerin/RANKL ratio in osteoblasts. Targeting TNFalpha in nAchR7(-/-) mice normalized both serum osteoprotegerin/RANKL ratios and bone mass. Administration of nicotine, an alpha7nAchR ligand, to wild-type mice increased serum RANKL levels. Thus, vagal nerve stimulation of macrophages via alpha7nAchR regulates bone mass by modulating osteoclast formation. |