Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts
Section snippets
Materials and methods
Materials. Eagle’s α-MEM, penicillin, and streptomycin were obtained from Invitrogen (Carlsbad, CA). Fetal calf serum (FCS) was purchased from Sanko Junyaku (Tokyo, Japan). Dexamethasone, 17β-estradiol, dihydrotestosterone, 1,25-dihydroxyvitamin D3, LiCl, and goat immunoglobulin (IgG) were purchased from Sigma (St. Louis, MI). Anti-β-catenin monoclonal antibody and anti-Dkk-1 goat polyclonal antibody were purchased from Transduction Laboratories (Lexington, KY) and Santa Cruz Biotechnology
Results
To investigate the effect of glucocorticoid on canonical Wnt signaling, we first examined whether glucocorticoid would affect the Tcf/Lef-dependent transcriptional activity by a Tcf-reporter gene (luciferase) assay in cultured osteoblasts (Fig. 1A). In primary cultured human osteoblasts, the addition of Wnt3a-conditioned medium (Wnt3a-CM) enhanced the Tcf/Lef-dependent transcriptional activity (approximately 3.5-fold). Dexamethasone suppressed the Wnt3a-induced Tcf/Lef-dependent transcriptional
Discussion
In the present study, we demonstrated that dexamethasone suppressed the Tcf/Lef-dependent canonical Wnt signaling pathway in primary cultured human osteoblasts. This effect was in part attributed to the increase of Dkk-1 expression by dexamethasone.
Glucocorticoid suppresses osteoblastic differentiation and proliferation by affecting multiple aspects of osteoblast function [1], [2], [3]. One well-known effect of glucocorticoid on osteoblast is the inhibition of the expression for Runx2/Cbfa1 [17]
Acknowledgments
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.
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