S-Space College of Dentistry/School of Dentistry (치과대학/치의학대학원) Dept. of Dentistry (치의학과) Journal Papers (저널논문_치의학과)
Msx2 is required for TNF-alpha-induced canonical Wnt signaling in 3T3-L1 preadipocytes
- Qadir, Abdul S.; Lee, Hye-Lim; Baek, Kyung Hwa; Park, Hyun-Jung; Ryoo, Hyun-Mo; Baek, Jeong-Hwa; Woo, Kyung Mi
- Issue Date
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.408, No.3, pp.399-404
- Tumor necrosis factor-alpha (TNF-alpha) is known to suppress adipocyte differentiation via a beta-catenin-dependent pathway. However, the mechanisms by which TNF-alpha induces Wnt/beta-catenin signaling pathway in adipocytes is unclear. Msx2, a homeobox transcription factor, is known to increase osteoblast differentiation through activation of the Wnt/beta-catenin pathway. Therefore, in the present study, we investigated whether TNF-alpha activates the Wnt/beta-catenin signaling pathway via the induction of Msx2 expression in 3T3-L1 preadipocytes. We found that TNF-alpha transiently increased Msx2 expression as well as the expression of canonical Wnt signaling molecules, including Wnt3a, Wnt7a, Wnt7b, Wnt10b, low-density lipoprotein receptor-related protein 5 (LRP5) and T-cell factor 1 (TCF1). Furthermore, TNF-alpha increased beta-catenin/TCF-dependent transcriptional activity. To better understand the role of Msx2 in Wnt signaling, we examined the effects of Msx2 overexpression and knockdown on Wnt/beta-catenin signaling. Msx2 overexpression alone significantly increased the levels of Wnt3a, Wnt7a, Wnt7b, Wnt10b, LRP5 and TCF1 expression, whereas knockdown of Msx2 using small interfering RNA prevented TNF-alpha-induced expression of Wnt signaling molecules. Taken together, the results of this study indicate that TNF-alpha enhances the Wnt/beta-catenin signaling pathway by inducing Msx2 expression, which in turn suppresses adipocytic differentiation. (C) 2011 Elsevier Inc. All rights reserved.
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