Glucocorticoid enhances the expression of dickkopf-1 in human osteoblasts: Novel mechanism of glucocorticoid-induced osteoporosis

Keizo Ohnaka, Hiroshi Taniguchi, Hisaya Kawate, Hajime Nawata, Ryoichi Takayanagi

Research output: Contribution to journalArticle

157 Citations (Scopus)

Abstract

To clarify the underlying mechanism of glucocorticoid-induced osteoporosis, we investigated the effect of glucocorticoid on the expression of dickkopf-1 (Dkk-1), an antagonist of Wnt signaling, in primary cultured human osteoblasts. Dexamethasone markedly induced the expression of mRNA for Dkk-1 in a dose- and time-dependent manner. The expression of Kremen1, a receptor for Dkk, did not change by the treatment with dexamethasone, while that of low-density lipoprotein receptor-related protein 5 (LRP5), a Wnt coreceptor, slightly decreased by the treatment with dexamethasone. Dexamethasone increased the transcriptional activity of the Dkk-1 gene promoter in human osteoblasts. Serial deletion and mutation analyses of the Dkk-1 promoter showed that one putative glucocorticoid responsive element-like sequence located from -788 to -774bp is essential for the enhancement of the Dkk-1 promoter activity by dexamethasone in human osteoblasts. Since the Wnt signal is now recognized as a crucial regulator for bone formation, the Dkk-1 enhanced by glucocorticoid may inhibit the Wnt signal in osteoblasts, which may be involved in the pathogenesis of glucocorticoid-induced osteoporosis.

Original languageEnglish
Pages (from-to)259-264
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume318
Issue number1
DOIs
Publication statusPublished - May 21 2004

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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