Gene array analysis of Wnt-regulated genes in C3H1OT1/2 cells
Gene array analysis of Wnt-regulated genes in C3H1OT1/2 cells
复制标题
DOI：
10.1016/j.bone.2005.01.007
复制
发表时间：
2005-04-01
期刊：
影响因子：
4.1
通讯作者：
Rawadi, G
中科院分区：
文献类型：
--
作者：
Jackson, A;Vayssière, B;Rawadi, G
Wnt/β-连环蛋白信号转导参与了大量的建模和重塑过程，包括细胞极性、细胞分化和细胞迁移。最近，Wnt通路在骨生物学中的作用已被证实。然而，Wnt蛋白调节骨形成的确切机制仍有待阐明。我们以前已经表明，Wnt途径介导诱导碱性磷酸酶，成骨细胞分化标志物，在多能间充质细胞C3 HIOT 1/2。在本研究中，我们进行了全基因组的表达分析，使用Affytek寡核苷酸芯片，以确定Wnt 3a诱导的基因表达谱在C3 H10 T1/2细胞。447 Wnt 3a调控基因的表达谱，分为不同的功能家族，在这里。我们的数据显示，Wnt 3a调节几个基因，参与成骨细胞和脂肪细胞分化。重要的是，Wnt 3a通过β-连环蛋白依赖性机制诱导骨保护素的表达，表明Wnt途径也可能影响破骨细胞生成。通过我们的表达谱数据的分析，我们已经建立了一个TaqMan面板作为一种工具，以快速比较由不同的刺激作用于Wnt/β-连环蛋白途径诱导的一组特定基因的表达谱。使用TaqMan面板，我们比较了C3 H10 T1/2细胞中Wnt 1，Wnt 2和Wnt 3a诱导的基因表达谱，以及两种不同的GSK-3 β抑制剂：LiCl和SB 216773。我们的数据表明，Wnt 1和Wnt 3a以类似的方式起作用，与Wnt 2不同。最后，我们发现LiCl和SB 216773在TaqMan面板中显示出不同的特征，证明它们对GSK-3 β具有不同的抑制作用。总之，本文提供的数据将有助于进一步理解Writ信号传导途径参与成骨细胞和脂肪细胞分化和功能的调节，此外，还将增强Wnt信号传导途径本身的现有知识（c）2005 Elsevier Inc. All rights reserved.
Wnt/beta-catenin signaling is involved in a large variety of modeling and remodeling processes including cell polarity, cell differentiation, and cell migration. Recently, a role of the Wnt pathway in bone biology has been demonstrated. However, the precise mechanism by which Wnt proteins regulate bone formation still remains to be elucidated. We have previously shown that the Wnt pathway mediates induction of alkaline phosphatase, an osteoblast differentiation marker, in the pluripotent mesenchymal cells C3HIOT1/2. In the present study, we performed a genome-wide expression analysis using Affymetrix oligonucleotide chips to determine the Wnt3a-induced gene expression profile in C3H10T1/2 cells. The expression profiles of 447 Wnt3a-regulated genes, classified into distinct functional families, are presented here. Our data reveal that Wnt3a regulates several genes that are involved in osteoblast and adipocyte differentiation. Importantly, Wnt3a induces the expression of osteoprotegerin by a beta-catenin dependent mechanism indicating that the Wnt pathway may also affect osteoclastogenesis. Through the analysis of our expression profiling data, we have established a TaqMan panel as a tool to rapidly compare the expression profiles of a specific set of genes induced by distinct stimuli acting in the Wnt/beta-catenin pathway. Using the TaqMan panel, we have compared the gene expression profiles induced by Wnt1, Wnt2, and Wnt3a in C3H10T1/2 cells, and also by two different GSK-3 beta inhibitors: LiCl and SB216773. Our data show that Wnt1 and Wnt3a act in a similar manner, distinct from Wnt2. Finally, we found that LiCl and SB216773 displayed different profiles in the TaqMan panel evidencing their distinct inhibitory action toward GSK-3 beta. Overall, data presented herein will aid further understanding of the involvement of the Writ signaling pathway in its regulation of osteoblast and adipocyte differentiation and function and, in addition, will enhance current knowledge of the Wnt signaling pathway itself (c) 2005 Elsevier Inc. All rights reserved.