Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts

Ohnaka Keizo, Mizuho Tanabe, Hisaya Kawate, Hajime Nawata, Ryoichi Takayanagi

Research output: Contribution to journalArticle

162 Citations (Scopus)

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 languageEnglish
Pages (from-to)177-181
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume329
Issue number1
DOIs
Publication statusPublished - Apr 1 2005

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TCF Transcription Factors
Osteoblasts
Dexamethasone
Glucocorticoids
Catenins
Glycogen Synthase Kinase 3
Calcitriol
Osteogenesis
Osteoporosis
Bone
Antibodies

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 journalArticle

Keizo, Ohnaka ; Tanabe, Mizuho ; Kawate, Hisaya ; Nawata, Hajime ; Takayanagi, Ryoichi. / Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts. In: Biochemical and Biophysical Research Communications. 2005 ; Vol. 329, No. 1. pp. 177-181.
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