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-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.
| Original language | English |
|---|---|
| Pages (from-to) | 177-181 |
| Number of pages | 5 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 329 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Apr 1 2005 |
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All Science Journal Classification (ASJC) codes
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts. / Keizo, Ohnaka; Tanabe, Mizuho; Kawate, Hisaya; Nawata, Hajime; Takayanagi, Ryoichi.
In: Biochemical and Biophysical Research Communications, Vol. 329, No. 1, 01.04.2005, p. 177-181.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts
AU - Keizo, Ohnaka
AU - Tanabe, Mizuho
AU - Kawate, Hisaya
AU - Nawata, Hajime
AU - Takayanagi, Ryoichi
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
VL - 329
SP - 177
EP - 181
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -