Artículo
A cholinergic neuroskeletal interface promotes bone formation during postnatal growth and exercise.
Autor/es | Gadomski, Stephen
Fielding, Claire García García, Andrés Korn, Claudia Kapeni, Chrysa Ashraf, Sadaf Villadiego Luque, Francisco Javier Toro Estévez, Raquel del Toledo Aral, Juan José Méndez Ferrer, Simón |
Departamento | Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica |
Fecha de publicación | 2022 |
Fecha de depósito | 2022-10-14 |
Publicado en |
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Resumen | The autonomic nervous system is a master regulator of homeostatic processes and stress responses. Sym pathetic noradrenergic nerve fibers decrease bone mass, but the role of cholinergic signaling in bone has
remained ... The autonomic nervous system is a master regulator of homeostatic processes and stress responses. Sym pathetic 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 un dergoes an interleukin-6 (IL-6)-induced cholinergic switch upon contacting the bone. A neurotrophic depen dency mediated through GDNF-family receptor-a2 (GFRa2) and its ligand, neurturin (NRTN), is established between sympathetic cholinergic fibers and bone-embedded osteocytes, which require cholinergic innerva tion 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-depen dent expansion of sympathetic cholinergic nerve fibers. Consequently, loss of cholinergic skeletal innerva tion reduces osteocyte survival and function, causing osteopenia and impaired skeletal adaptation to mod erate exercise. These results uncover a cholinergic neuro-osteocyte interface that regulates skeletogenesis and skeletal turnover through bone-anabolic effects. |
Cita | Gadomski, S., Fielding, C., García García, A., Korn, C., Kapeni, C., Ashraf, S.,...,Méndez Ferrer, S. (2022). A cholinergic neuroskeletal interface promotes bone formation during postnatal growth and exercise.. Cell Stem Cell, 29 (4), 528-544.e9. https://doi.org/10.1016/j.stem.2022.02.008. |
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A cholinergic neuroskeletal.pdf | 9.302Mb | [PDF] | Ver/ | |