Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts

Autor: Hisaya Kawate, Ryoichi Takayanagi, Keizo Ohnaka, Mizuho Tanabe, Hajime Nawata
Rok vydání: 2005
Předmět:
Transcription
Genetic
Biochemistry
Dexamethasone
Cytosol
Genes
Reporter
Microscopy
Confocal
biology
Wnt signaling pathway
Osteoblast
Cell biology
medicine.anatomical_structure
embryonic structures
Intercellular Signaling Peptides and Proteins
Glucocorticoid
medicine.drug
Plasmids
Subcellular Fractions
Transcriptional Activation
medicine.medical_specialty
animal structures
Genetic Vectors
Green Fluorescent Proteins
Biophysics
Active Transport
Cell Nucleus
Transfection
Cell Line
Wnt3 Protein
Adjuvants
Immunologic
Calcitriol
Internal medicine
Wnt3A Protein
medicine
Humans
Glycogen synthase
Enhancer
Molecular Biology
Glucocorticoids
Cell Nucleus
Osteoblasts
Dose-Response Relationship
Drug
Proteins
Cell Biology
body regions
Wnt Proteins
Endocrinology
Cell culture
biology.protein
Osteoporosis
Lithium Chloride
WNT3A
Zdroj: Biochemical and biophysical research communications. 329(1)
ISSN: 0006-291X
Popis: 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-3beta, 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 beta-catenin accumulated by Wnt3a and also inhibited the nuclear translocation of beta-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.
Databáze: OpenAIRE
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