Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts

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

Research output: Contribution to journalArticle

174 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

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this