Wnt-3a regulates chondrocyte differentiation via c-Jun/AP-1 pathway
Wnt-3a regulates chondrocyte differentiation via c-Jun/AP-1 pathway
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DOI：
10.1016/j.febslet.2005.07.067
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发表时间：
2005-08-29
期刊：
影响因子：
3.5
通讯作者：
Chun, JS
中科院分区：
文献类型：
--
作者：
Hwang, SG;Yu, SS;Chun, JS
我们之前的研究表明，白细胞介素 (IL)-1 beta 诱导软骨细胞中多种 Wnt 蛋白的表达，并通过 c-Jun/激活蛋白-1 (AP-1) 途径导致软骨细胞去分化。本研究检验了 Wnt-3a 是否通过 e-Jun/AP-1 途径导致软骨细胞去分化。 Wnt-3a 通过以不依赖于 P-连环蛋白转录活性的方式稳定细胞间粘附来抑制间充质细胞的软骨形成。 Wnt-3a 还通过刺激 β-连环蛋白-T 细胞因子/淋巴增强因子 (Tcf/Lef) 复合物的转录活性来诱导关节软骨细胞去分化。在软骨细胞中，Wnt-3a 引起 c-Jun 的表达及其被 c-Jun N 末端激酶 (JNK) 磷酸化，从而激活 AP-1。 AP-1激活抑制Sox-9的表达，Sox-9是调节11型胶原蛋白表达的主要转录因子。总的来说，我们的结果表明，Wnt-3a 通过稳定细胞间粘附来抑制软骨形成，并通过激活 β-catenin-Tcf/Lef 转录复合物和 c-Jun/AP-1 途径引起软骨细胞去分化。 (c) 2005 年欧洲生化学会联合会。由 Elsevier B.V. 出版。保留所有权利。
Our previous study indicated that interleukin (IL)-1 beta induces expression of several Wnt proteins in chondrocytes and causes chondrocyte dedifferentiation via the c-Jun/activator protein-1 (AP-1) pathway. This study examined whether Wnt-3a causes chondrocyte dedifferentiation via the e-Jun/AP-1 pathway. Wnt-3a inhibited chondrogenesis of mesenchymal cells by stabilizing cell-cell adhesion in a manner independent of P-catenin transcriptional activity. Wnt-3a also induced dedifferentiation of articular chondrocytes by stimulating the transcriptional activity of beta-catenin-T cell-factor/lymphoid-enhancer-factor (Tcf/Lef) complex. In chondrocytes, Wnt-3a caused the expression of c-Jun and its phosphorylation by c-Jun N-terminal kinase (JNK), resulting in activation of AP-1. AP-I activation suppressed the expression of Sox-9, a major transcription factor regulating type 11 collagen expression. Collectively, our results suggest that Wnt-3a inhibits chondrogenesis by stabilizing cell-cell adhesion and that it causes dedifferentiation of chondrocytes by activating of beta-catenin-Tcf/Lef transcriptional complex and the c-Jun/AP-1 pathway. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.