title: Inhibition of Wnt/β-catenin signaling by dexamethasone promotes adipocyte differentiation in mesenchymal progenitor cells, ROB-C26.
abstract: Dexamethasone (Dex) stimulates the differentiation of mesenchymal progenitor cells into adipocytes and osteoblasts. However, the mechanisms underlying Dex-induced differentiation have not been clearly elucidated. We examined the effect of Dex on the expression and activity of Wnt/β-catenin signal-related molecules in a clonal mesenchymal progenitor cell line, ROB-C26 (C26). Dex induced the mRNA expression of Wnt antagonists, dickkopf-1 (Dkk-1), and Wnt inhibitory factor (WIF)-1. Immunocytochemical analysis showed that the downregulation of β-catenin protein expression by Dex occured concomitantly with the increased expression of the PPARγ protein. Dex decreased phosphorylation of Ser9-GSK3β and expression of active β-catenin protein. To examine the effects of Dex on Wnt/β-catenin activity, we used immunocytochemistry to analyze TCF/LEF-mediated transcription during Dex-induced adipogenesis in Wnt indicator (TOPEGFP) C26 cells. Our results demonstrated that Dex repressed TCF/LEF-mediated transcription, but induced adipocyte differentiation. Treatment with a GSK3β inhibitor attenuated Dex-induced inhibition of TCF/LEF-mediated transcriptional activity, but suppressed Dex-induced adipocyte differentiation, indicating that adipocyte differentiation and inhibition of Wnt/β-catenin activity by Dex are mediated by GSK3β activity. Furthermore, β-catenin knockdown not only suppressed Dex-induced ALP-positive osteoblasts differentiation but also promoted Dex-induced adipocytes differentiation. These results suggest that inhibition of β-catenin expression by Dex promotes the differentiation of mesenchymal progenitor cells into adipocytes.
authors.affiliation: Department of Anatomy, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyodaku, Tokyo 101-8310, Japan. oomura@dent.nihon-u.ac.jp
authors.forename: Masako
authors.initials: M
authors.lastname: Naito
authors.forename: Kazuki
authors.initials: K
authors.lastname: Omoteyama
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Mikami
authors.forename: Tomihisa
authors.initials: T
authors.lastname: Takahashi
authors.forename: Minoru
authors.initials: M
authors.lastname: Takagi
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects*; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D020868:Gene Silencing; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship; D051153:Wnt Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051176:beta Catenin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C531384:Dkk1 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051153:Wnt Proteins; D051176:beta Catenin; D003907:Dexamethasone