Msx2 is required for TNF-alpha-induced canonical Wnt signaling in 3T3-L1 preadipocytes

作者：Qadir Abdul S; Lee Hye Lim; Baek Kyung Hwa; Park Hyun Jung; Woo Kyung Mi; Ryoo Hyun Mo; Baek Jeong Hwa^*

来源：Biochemical and Biophysical Research Communications, 2011, 408(3): 399-404.

DOI：10.1016/j.bbrc.2011.04.029

• Tumor necrosis factor-alpha
• Msx2
• Wnt signaling
• beta-catenin
• Adipocyte

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.

• 出版日期2011-5-13