title: Msx2 is required for TNF-α-induced canonical Wnt signaling in 3T3-L1 preadipocytes.
abstract: Tumor necrosis factor-α (TNF-α) is known to suppress adipocyte differentiation via a β-catenin-dependent pathway. However, the mechanisms by which TNF-α induces Wnt/β-catenin signaling pathway in adipocytes is unclear. Msx2, a homeobox transcription factor, is known to increase osteoblast differentiation through activation of the Wnt/β-catenin pathway. Therefore, in the present study, we investigated whether TNF-α activates the Wnt/β-catenin signaling pathway via the induction of Msx2 expression in 3T3-L1 preadipocytes. We found that TNF-α 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-α increased β-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/β-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-α-induced expression of Wnt signaling molecules. Taken together, the results of this study indicate that TNF-α enhances the Wnt/β-catenin signaling pathway by inducing Msx2 expression, which in turn suppresses adipocytic differentiation.
authors.affiliation: Department of Molecular Genetics, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749, Republic of Korea.
authors.forename: Abdul S
authors.initials: AS
authors.lastname: Qadir
authors.forename: Hye-Lim
authors.initials: HL
authors.lastname: Lee
authors.forename: Kyung Hwa
authors.initials: KH
authors.lastname: Baek
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Park
authors.forename: Kyung Mi
authors.initials: KM
authors.lastname: Woo
authors.forename: Hyun-Mo
authors.initials: HM
authors.lastname: Ryoo
authors.forename: Jeong-Hwa
authors.initials: JH
authors.lastname: Baek
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; C084119:MSX2 protein; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D051153:Wnt Proteins; D051176:beta Catenin