Roles of Wnt/β-catenin signaling in adipogenic differentiation potential of adipose-derived mesenchymal stem cells
Roles of Wnt/β-catenin signaling in adipogenic differentiation potential of adipose-derived mesenchymal stem cells
复制标题
DOI：
10.1016/j.mce.2008.05.005
复制
发表时间：
2008-09-10
影响因子：
4.1
通讯作者：
Yang, Gong-She
中科院分区：
文献类型：
--
作者：
Li, Hui-Xia;Luo, Xiao;Yang, Gong-She
Wnt/beta-catenin信号通路通过调节靶基因的表达来控制各种细胞的分化。β-catenin在Wnt/β-catenin信号通路中起核心作用。为了研究脂肪间充质干细胞（AMSCs）命运决定的分子机制，我们研究了Wnt/β-catenin信号通路的两个关键成员Wnt 3a和β-catenin在猪AMSCs成脂分化中的作用。我们证明Wnt 3a蛋白可以抑制体外培养的猪AMSCs的成脂分化。通过稳定细胞质中的β-连环蛋白并持续用LiCl处理，AMSC的成脂分化也被抑制，成骨被刺激。相反，AMSC中β-连环蛋白的缺失增强了脂肪形成分化并挽救了LiCl诱导的抗脂肪形成。此外，CCAAT/增强子结合蛋白-α（C/EBP α）和过氧化物酶体增殖物激活受体-γ（PPAR γ）的相互激活在Wnt 3a或LiCl的存在下被抑制，但β-连环蛋白的基因沉默增加。综上所述，我们的研究表明Wnt/β-catenin信号通路抑制脂肪细胞向成骨细胞的分化潜能，并改变细胞从脂肪细胞向成骨细胞的命运。(c)2008爱思唯尔爱尔兰有限公司保留所有权利。
Wnt/beta-catenin signaling pathway controls differentiation of various cells by regulating the expression of target genes. beta-Catenin plays a central role in Wnt/beta-catenin signaling pathway. To investigate the molecular mechanisms of fate determination in adipose-derived mesenchymal stem cells (AMSCs), we investigated effects of Wnt3a and beta-catenin, two key members of the Wnt/beta-catenin signaling, in adipogenic differentiation of porcine AMSCs. We demonstrated that Wnt3a protein can inhibit the adipogenic differentiation of porcine AMSCs in vitro culture. By stabilization of cytoplasmic beta-catenin with continuous treatment by LiCl, the adipogenic differentiation of AMSCs was also suppressed and the osteogenesis was stimulated. In contrast, a loss of beta-catenin in AMSCs enhanced the adipogenic differentiation and rescued LiCl-induced anti-adipogenesis. In addition, the mutual activation of CCAAT/enhancer-binding protein-alpha (C/EBP alpha) and peroxisome proliferator-activated receptor-gamma (PPAR gamma) were repressed in the presence of Wnt3a or LiCl, but increased in the gene silencing of beta-catenin. Taken together, our study indicated that Wnt/beta-catenin signaling pathway inhibited the adipogenic differentiation potential and alter the cell fate from adipocytes to osteoblasts. (c) 2008 Elsevier Ireland Ltd. All rights reserved.