Bone remodeling – the lifelong process of bone removal and formation – is tightly regulated. Recent studies have suggested a role for the sympathetic (“fight or flight”) nervous system in bone metabolism, but the contribution of endogenous norepinephrine (NE, the neurotransmitter released by sympathetic nerves) is unclear.
Florent Elefteriou, Ph.D., Yun Ma, M.D., Ph.D., and colleagues have now demonstrated that bone-forming osteoblast cells – like neurons – express active norepinephrine transporters (NET) that remove NE from outside the cells. They showed that drugs that block NET induce bone loss in wild-type mice, and that mice without NET have reduced bone formation and increased bone removal.
The findings, reported Oct. 18 in the Journal of Biological Chemistry, suggest that NET-mediated clearance of endogenous NE by neurons and bone cells plays an important role in the regulation of bone remodeling. The findings also suggest that drugs that block NET activity, which are used to treat depression and attention deficit hyperactivity disorder (ADHD), may have deleterious effects on the skeleton.
This research was supported by National Institutes of Health grants DK082471 and TR000445.