RT Journal Article
T1 A cholinergic neuroskeletal interface promotes bone formation during postnatal growth and exercise.
A1 Gadomski, Stephen
A1 Fielding, Claire
A1 Garcia-Garcia, Andres
A1 Korn, Claudia
A1 Kapeni, Chrysa
A1 Ashraf, Sadaf
A1 Villadiego, Javier
A1 Toro, Raquel Del
A1 Domingues, Olivia
A1 Skepper, Jeremy N
A1 Michel, Tatiana
A1 Zimmer, Jacques
A1 Sendtner, Regine
A1 Dillon, Scott
A1 Poole, Kenneth E S
A1 Holdsworth, Gill
A1 Sendtner, Michael
A1 Toledo-Aral, Juan J
A1 De Bari, Cosimo
A1 McCaskie, Andrew W
A1 Robey, Pamela G
A1 Mendez-Ferrer, Simon
K1 anabolic
K1 autonomic
K1 bone
K1 cholinergic
K1 development
K1 exercise
K1 neuroskeletal
K1 osteocyte
K1 skeletal
K1 sympathetic
AB The autonomic nervous system is a master regulator of homeostatic processes and stress responses. Sympathetic noradrenergic nerve fibers decrease bone mass, but the role of cholinergic signaling in bone has remained largely unknown. Here, we describe that early postnatally, a subset of sympathetic nerve fibers undergoes an interleukin-6 (IL-6)-induced cholinergic switch upon contacting the bone. A neurotrophic dependency mediated through GDNF-family receptor-α2 (GFRα2) and its ligand, neurturin (NRTN), is established between sympathetic cholinergic fibers and bone-embedded osteocytes, which require cholinergic innervation for their survival and connectivity. Bone-lining osteoprogenitors amplify and propagate cholinergic signals in the bone marrow (BM). Moderate exercise augments trabecular bone partly through an IL-6-dependent expansion of sympathetic cholinergic nerve fibers. Consequently, loss of cholinergic skeletal innervation reduces osteocyte survival and function, causing osteopenia and impaired skeletal adaptation to moderate exercise. These results uncover a cholinergic neuro-osteocyte interface that regulates skeletogenesis and skeletal turnover through bone-anabolic effects.
PB Cell Press
YR 2022
FD 2022-03-10
LK http://hdl.handle.net/10668/22525
UL http://hdl.handle.net/10668/22525
LA en
NO Gadomski S, Fielding C, García-García A, Korn C, Kapeni C, Ashraf S, et al. A cholinergic neuroskeletal interface promotes bone formation during postnatal growth and exercise. Cell Stem Cell. 2022 Apr 7;29(4):528-544.e9.
DS RISalud
RD Apr 20, 2025