Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts.
Biochem Biophys Res Commun
; 329(1): 177-81, 2005 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-15721290
ABSTRACT
To explore the mechanism of glucocorticoid-induced osteoporosis, we investigated the effect of glucocorticoid on canonical Wnt signaling that emerged as a novel key pathway for promoting bone formation. Wnt3a increased the T-cell factor (Tcf)/lymphoid enhancer factor (Lef)-dependent transcriptional activity in primary cultured human osteoblasts. Dexamethasone suppressed this transcriptional activity in a dose-dependent manner, while 1,25-dihydroxyvitamin D3 increased this transcriptional activity. LiCl, an inhibitor of glycogen synthase kinase-3beta, also enhanced the Tcf/Lef-dependent transcriptional activity, which was, however, not inhibited by dexamethasone. The addition of anti-dickkopf-1 antibody partially restored the transcriptional activity suppressed by dexamethasone. Dexamethasone decreased the cytosolic amount of beta-catenin accumulated by Wnt3a and also inhibited the nuclear translocation of beta-catenin induced by Wnt3a. These data suggest that glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts, partially through the enhancement of the dickkopf-1 production.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Osteoblastos
/
Peptídeos e Proteínas de Sinalização Intercelular
/
Glucocorticoides
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article