The canonical Wnt signaling pathway promotes chondrocyte differentiation in a Sox9-dependent manner
The canonical Wnt signaling pathway promotes chondrocyte differentiation in a Sox9-dependent manner
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DOI：
10.1016/j.bbrc.2005.06.041
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发表时间：
2005-08-12
影响因子：
3.1
通讯作者：
Chung, U
中科院分区：
文献类型：
--
作者：
Yano, F;Kugimiya, F;Chung, U
为了更好地了解规范的WRIT信号通路在软骨发育中的作用，我们在未分化的间充质细胞、软骨细胞和原代软骨细胞中表达了淋巴增强因子-1(LEF-1)的组成活性(Ca)或显性负性(DN)形式，并检测了软骨分化和肥大的标志物。Calef-1和经典通路激活剂Lig同时促进软骨分化和肥大，而dnLEF-1和P-catenin的基因沉默抑制了LiCl的促进作用。为了研究这些效应是否依赖于软骨发育的主要调节因子Sox9，我们用该途径刺激了Sox9缺陷的ES细胞。在野生型细胞中，Calef-1和LiCl2促进成软骨细胞分化和肥大，但在Sox9缺乏的细胞中不能。重组腺病毒表达Sox9可恢复Sox9缺陷细胞的免疫应答。因此，典型的Wnt信号通路以Sox9依赖的方式促进软骨细胞分化。(C)2005 Elsevier Inc.保留所有权利。
To better understand the role of the canonical Writ signaling pathway in cartilage development, we adenovirally expressed a constitutively active (ca) or a dominant negative (dn) form of lymphoid enhancer factor-1 (LEF-1), the main nuclear effector of,the pathway, in undifferentiated mesenchymal cells, chondrogenic cells, and primary chondrocytes, and examined the expression of markers for chondrogenic differentiation and hypertrophy. caLEF-1 and LiG, an activator of the canonical pathway, promoted both chondrogenic differentiation and hypertrophy, whereas dnLEF-1 and the gene silencing of P-catenin suppressed LiCl-promoted effects. To investigate whether these effects were dependent on Sox9, a master regulator of cartilage development, we stimulated Sox9-deficient ES cells with the pathway. caLEF-1 and LiCl promoted both chondrogenic differentiation and hypertrophy in wildtype, but not in Sox9-deficient, cells. The response of Sox9-deficient cells was restored by the adenoviral expression of Sox9. Thus, the canonical Wnt signaling pathway promotes chondrocyte differentiation in a Sox9-dependent manner. (c) 2005 Elsevier Inc. All rights reserved.