NGF-TrkA signaling in sensory nerves is required for skeletal adaptation to mechanical loads in mice.
Proc Natl Acad Sci U S A
; 114(18): E3632-E3641, 2017 05 02.
Article
em En
| MEDLINE
| ID: mdl-28416686
ABSTRACT
Sensory nerves emanating from the dorsal root extensively innervate the surfaces of mammalian bone, a privileged location for the regulation of biomechanical signaling. Here, we show that NGF-TrkA signaling in skeletal sensory nerves is an early response to mechanical loading of bone and is required to achieve maximal load-induced bone formation. First, the elimination of TrkA signaling in mice harboring mutant TrkAF592A alleles was found to greatly attenuate load-induced bone formation induced by axial forelimb compression. Next, both in vivo mechanical loading and in vitro mechanical stretch were shown to induce the profound up-regulation of NGF in osteoblasts within 1 h of loading. Furthermore, inhibition of TrkA signaling following axial forelimb compression was observed to reduce measures of Wnt/ß-catenin activity in osteocytes in the loaded bone. Finally, the administration of exogenous NGF to wild-type mice was found to significantly increase load-induced bone formation and Wnt/ß-catenin activity in osteocytes. In summary, these findings demonstrate that communication between osteoblasts and sensory nerves through NGF-TrkA signaling is essential for load-induced bone formation in mice.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Osteogênese
/
Células Receptoras Sensoriais
/
Músculo Esquelético
/
Receptor trkA
/
Fator de Crescimento Neural
/
Via de Sinalização Wnt
Limite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2017
Tipo de documento:
Article