TY - JOUR
T1 - Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts
AU - Ohnaka, Keizo
AU - Tanabe, Mizuho
AU - Kawate, Hisaya
AU - Nawata, Hajime
AU - Takayanagi, Ryoichi
N1 - Funding Information:
This work was supported in part by Grants-in-Aid for Scientific Research (B), Scientific Research (C) and Exploratory Research, and a grant for the 21st Century Center of Excellence (COE) Program (Kyushu University) from the Japanese Ministry of Education, Culture, Sports, Science and Technology.
PY - 2005/4/1
Y1 - 2005/4/1
N2 - 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-3β, 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 β-catenin accumulated by Wnt3a and also inhibited the nuclear translocation of β-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.
AB - 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-3β, 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 β-catenin accumulated by Wnt3a and also inhibited the nuclear translocation of β-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.
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U2 - 10.1016/j.bbrc.2005.01.117
DO - 10.1016/j.bbrc.2005.01.117
M3 - Article
C2 - 15721290
AN - SCOPUS:13844272561
VL - 329
SP - 177
EP - 181
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -