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Inhibition of Wnt/β-catenin signaling by dexamethasone promotes adipocyte differentiation in mesenchymal progenitor cells, ROB-C26

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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.

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Acknowledgments

The TOPEGFP reporter plasmid was kindly provided by Dr. M. Oshima (Cancer Research Institute, Kanazawa University, Japan). This work was supported in part by research grant from the dental research center (M.T) and Grant-in-Aid for Young Scientists (B) from the Ministry of Education, Culture, Sports, Science and Technology, Japan (M.N., 21791799).

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Authors and Affiliations

  1. Department of Anatomy, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyodaku, Tokyo, 101-8310, Japan

    Masako Naito, Kazuki Omoteyama, Yoshikazu Mikami, Tomihisa Takahashi & Minoru Takagi

  2. Division of Functional Morphology, Dental Research Center, Nihon University School of Dentistry, Tokyo, 101-8310, Japan

    Masako Naito, Kazuki Omoteyama, Yoshikazu Mikami, Tomihisa Takahashi & Minoru Takagi

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  1. Masako Naito
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  2. Kazuki Omoteyama
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  5. Minoru Takagi
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Correspondence to Masako Naito.

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Naito, M., Omoteyama, K., Mikami, Y. et al. Inhibition of Wnt/β-catenin signaling by dexamethasone promotes adipocyte differentiation in mesenchymal progenitor cells, ROB-C26. Histochem Cell Biol 138, 833–845 (2012). https://doi.org/10.1007/s00418-012-1007-3

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