Cho Seo-Hyun, Oh Chun-Do, Kim Song-Ja, Kim Il-Chul, Chun Jang-Soo
Department of Life Sciences, Kwangju Institute of Science and Technology, Gwangju 500-712, Korea.
J Cell Biochem. 2003 Jul 1;89(4):837-47. doi: 10.1002/jcb.10553.
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.
视黄酸（RA）是一种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形成分化，还会导致已分化软骨细胞表型的丧失。本研究探讨了RA调节软骨形成的潜在机制。在软骨化的间充质细胞中进行RA处理不会影响软骨前凝聚，但会阻止从软骨前凝聚到软骨结节形成的进程。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。从软骨前凝聚到软骨结节的进程需要下调N-钙黏蛋白的表达。然而，RA处理导致N-钙黏蛋白及其相关蛋白（包括α-连环蛋白和β-连环蛋白）持续表达，这表明这些分子表达的调节与RA诱导的软骨形成抑制有关。细胞松弛素D（CD）破坏肌动蛋白细胞骨架可阻断RA诱导的细胞黏附分子持续表达并克服RA诱导的软骨形成抑制，这一观察结果支持了这一假设。综上所述，我们的结果表明RA通过在软骨前凝聚后阶段稳定细胞间相互作用来抑制软骨形成。
