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Up-regulation of Axin2 by dexamethasone promotes adipocyte differentiation in ROB-C26 mesenchymal progenitor cells

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Abstract

Dexamethasone (Dex) regulates osteoblastic and adipocytic differentiation in mesenchymal progenitor cells through regulation of Wnt/β-catenin signaling. To elucidate the regulatory mechanisms underlying the effects of Dex, we examine the expression of Axin2, which is an intracellular inhibitor of Wnt/β-catenin signaling, in ROB-C26 clonal mesenchymal progenitor cells (C26). We observed the induction of Axin2 mRNA in C26 cells in response to Dex treatment. Treatment with a glucocorticoid receptor (GR) antagonist, mifepristone, showed that Dex-induced up-regulation of Axin2 is mediated by the GR. In the absence of Dex, gene silencing by using Axin2-targeted short hairpin RNA increased the number of alkaline phosphatase (ALP)-positive and nuclear β-catenin-positive cells and ALP activity. In the presence of Dex, Axin2 knockdown resulted in an increased number of ALP-positive and nuclear β-catenin-positive cells. Furthermore, Axin2 knockdown in Dex-treated cells suppressed adipocyte differentiation (as determined by reduced Oil Red O staining), reduced the number of PPARγ-positive and aP2-positive cells and decreased the mRNA expression of PPARγ2 and aP2. These results suggest that Axin2 plays a key role in adipocyte and osteoblastic differentiation by controlling β-catenin expression.

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Authors and Affiliations

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

    Masako Naito, Yoshikazu Mikami, Minoru Takagi & Tomihisa Takahashi

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

    Masako Naito, Yoshikazu Mikami, Minoru Takagi & Tomihisa Takahashi

Authors
  1. Masako Naito
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  2. Yoshikazu Mikami
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  3. Minoru Takagi
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  4. Tomihisa Takahashi
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Correspondence to Masako Naito.

Additional information

This work was supported in part by a research grant from the dental research center (M.T.), Sato Fund, Nihon University School of Dentistry (T.T.) and Grant-in-Aid for Young Scientists (B) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (M.N., 21791799).

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Naito, M., Mikami, Y., Takagi, M. et al. Up-regulation of Axin2 by dexamethasone promotes adipocyte differentiation in ROB-C26 mesenchymal progenitor cells. Cell Tissue Res 354, 761–770 (2013). https://doi.org/10.1007/s00441-013-1696-5

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  • DOI: https://doi.org/10.1007/s00441-013-1696-5

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