Retinoic acid inhibits chondrogenesis of mesenchymal cells by sustaining expression of N-cadherin and its associated proteins
Retinoic acid inhibits chondrogenesis of mesenchymal cells by sustaining expression of N-cadherin and its associated proteins
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DOI：
10.1002/jcb.10553
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发表时间：
2003-07-01
影响因子：
4
通讯作者：
Chun, JS
中科院分区：
文献类型：
--
作者：
Cho, SH;Oh, CD;Chun, JS
视黄酸（RA）是众所周知的软骨细胞表型调节剂。 RA 抑制间充质细胞的软骨分化，还会导致分化软骨细胞表型的丧失。本研究调查了 RA 调节软骨形成的机制。软骨化间充质细胞中的 RA 治疗不影响软骨前凝结，但阻止软骨前凝结到软骨结节形成的进展。 RA 的这种抑制作用独立于蛋白激酶 C 和细胞外信号调节蛋白激酶，它们分别是软骨结节形成的正调节因子和负调节因子。从软骨前凝结到软骨结节的进展需要下调 N-钙粘蛋白的表达。然而，RA治疗引起N-钙粘蛋白及其相关蛋白（包括α-和β-连环蛋白）的持续表达，表明这些分子表达的调节与RA诱导的软骨形成抑制相关。这一假设得到了以下观察结果的支持：细胞松弛素 D (CD) 对肌动蛋白细胞骨架的破坏阻断了 RA 诱导的细胞粘附分子的持续表达，并克服了 RA 诱导的软骨形成抑制。综上所述，我们的结果表明 RA 通过稳定软骨前凝结阶段的细胞间相互作用来抑制软骨形成。 (C) 2003 Wiley-Liss, Inc.
Retinoic acid (RA) is a well-known regulator of chondrocyte phenotype. RA inhibits chondrogenic differentiation of mesenchymal cells and also causes loss of differentiated chondrocyte phenotype. The present study investigated the mechanisms underlying RA regulation of chondrogenesis. RA treatment in chondrifying mesenchymal cells did not affect precartilage condensation, but blocked progression from precartilage condensation to cartilage nodule formation. This inhibitory effect of RA was independent of protein kinase C and extracellular signal-regulated protein kinase, which are positive and negative regulators of cartilage nodule formation, respectively. The progression from precartilage condensation to cartilage nodule requires downregulation of N-cadherin expression. However, RA treatment caused sustained expression of N-cadherin and its associated proteins including alpha- and beta-catenin suggesting that modulation of expression of these molecules is associated with RA-induced inhibition of chondrogenesis. This hypothesis was supported by the observation that disruption of the actin cytoskeleton by cytochalasin D (CD) blocks RA-induced sustained expression of cell adhesion molecules and overcomes RA-induced inhibition of chondrogenesis. Taken together, our results suggest RA inhibits chondrogenesis by stabilizing cell-to-cell interactions at the post-precartilage condensation stage. (C) 2003 Wiley-Liss, Inc.