All-trans retinoic acid inhibited chondrogenesis of mouse embryonic palate mesenchymal cells by down-regulation of TGF-β/Smad signaling
All-trans retinoic acid inhibited chondrogenesis of mouse embryonic palate mesenchymal cells by down-regulation of TGF-β/Smad signaling
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DOI：
10.1016/j.bbrc.2005.12.100
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发表时间：
2006-02-17
影响因子：
3.1
通讯作者：
Xing, Y
中科院分区：
文献类型：
--
作者：
Yu, ZL;Xing, Y
软骨形成是腭发育的关键步骤。全反式视黄酸 (atRA) 是一种维生素 A 衍生物，是已知的腭裂致畸效应物。在这里，我们评估了 atRA 油对小鼠胚胎腭间充质 (MEPM) 细胞的骨/软骨分化的影响。 MEPM 细胞，处于高密度微质量环境中。以类似于肢体来源的间充质细胞的方式经历活跃的软骨形成，并作为研究腭形成过程中调节软骨形成的机制的有效模型系统。 atRA处理的MEPM微团表达相对较高水平的成骨细胞基因标记物（碱性磷酸酶和1型胶原蛋白）和较低水平的软骨细胞基因标记物（II型胶原蛋白和聚集蛋白聚糖）。由于转化生长因子-β3（TGF-β3）是体内和体外条件下胚胎间充质细胞软骨形成的重要生长因子，因此我们探讨了atRA对TGF-β3信号传导的影响途径。通过实时 RT-PCR 测定，atRA 导致 TGF-β 3 mRNA 表达增加，并且 TGF-β II 型受体 (T beta RII) 瞬时减少。进一步研究表明atRA抑制Smad2和Smad3的磷酸化并增加Smad7的表达。通过用 Smad7 Delta C 突变体或组成型活性 T beta RII 逆转录病毒载体转染来激活 Smad 途径，消除了 atRA 诱导的软骨形成抑制，如阿尔新蓝染色所示。这表明 Smad 信号传导对于这种反应至关重要。总而言之，这些数据首次证明了通过调节 TGF-β 3 途径在 RA 诱导的软骨形成中发挥作用，并表明 TPRII/Smad 在类维生素A诱导的腭裂中发挥作用。 (c) 2005 年爱思唯尔文件。版权所有。
Chondrogenesis is a critical step in palatogenesis. All-trans retinoic acid (atRA), a vitamin A derivative, is a known teratogenic effector of cleft palate. Here, we evaluated the effects of atRA oil the osteo-/chondrogenic differntiation Of Mouse embryonic palate mesenchymal (MEPM) cells. MEPM cells, in a high-density micromass environment. undergo active chondrogenesis in a manner analogous to that of limb-derived mesenchymal cells, and served its a valid model system to investigate the mechanisms regulating chondrogenesis during palatogenesis. atRA-treated MEPM micromass expressed relatively higher levels of osteoblastic gene markers (alkaline phosphatase and collagen type 1) and lower levels of chondrocytic gene markers (collagen type II and aggrecan), As transforming growth factor-beta 3 (TGF-beta 3) is an essential growth factor for chondrogenesis of embryonic mesenchymal cells both in in vivo and in vitro conditions, we thereby explored the effects of atRA on TGF-beta 3 signaling pathway. atRA led to an increase in mRNA expression of TGF-beta 3 and an instantaneous decrease in TGF-beta type II receptor (T beta RII) as determined by real-time RT-PCR. Further study showed that atRA inhibited phosphorylation of Smad2 and Smad3 and increased Smad7 expression. Activation of the Smad pathways by transfection with Smad7 Delta C Mutant or constitutively active T beta RII retroviral vector abolished atRA-induced inhibition of chondrogenesis as indicated by Alcian blue staining.. indicating that Smad signaling is essential for this response. Taken together, these data for the first time demonstrated a role for RA-induced hypochondrogenesis through regulation of the TGF-beta 3 pathway and Suggested a role for TPRII/Smad in retinoid-induced cleft palate. (c) 2005 Elsevier file. All rights reserved.