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首页> 外文期刊>Journal of Cellular Physiology >Bone morphogenetic protein-2 modulation of chondrogenic differentiation in vitro involves gap junction-mediated intercellular communication.
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Bone morphogenetic protein-2 modulation of chondrogenic differentiation in vitro involves gap junction-mediated intercellular communication.

机译:骨形成protein-2调制chondrogenic体外分化涉及间隙连接调控细胞间沟通。

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摘要

Undifferentiated mesenchymal cells in the limb bud integrate a complex array of local and systemic signals during the process of cell condensation and chondrogenic differentiation. To address the relationship between bone morphogenetic protein (BMP) signaling and gap junction-mediated intercellular communication, we examined the effects of BMP-2 and a gap junction blocker 18 alpha glycyrrhetinic acid (18alpha-GCA) on mesenchymal cell condensation and chondrogenic differentiation in an in vitro chondrogenic model. We find that connexin43 protein expression significantly correlates with early mesenchymal cellular condensation and chondrogenesis in high-density limb bud cell culture. The level of connexin43 mRNA is maximally upregulated 48 h after treatment with recombinant human BMP-2 with corresponding changes in protein expression. Inhibition of gap junction-mediated intercellular communication with 2.5 microM 18alpha-GCA decreases chondrogenic differentiation by 50% at 96 h without effects on housekeeping genes. Exposure to 18alpha-GCA for only the first 24-48 h after plating does not affect condensation or later chondrogenic differentiation suggesting that gap junction-mediated intercellular communication is not critical for the initial phase of condensation but is important for the onset of differentiation. 18alpha-GCA can also block the chondrogenic effects of BMP-2 without effects on cell number or connexin43 expression. These observations demonstrate 18alpha-GCA-sensitive regulation of intercellular communication in limb mesenchymal cells undergoing chondrogenic differentiation and suggest that BMP-2 induced chondrogenic differentiation may be mediated in part through the modulation of connexin43 expression and gap junction-mediated intercellular communication.
机译:肢芽的未分化间充质细胞一系列复杂的局部和系统集成细胞信号过程中凝结和chondrogenic分化。骨形成蛋白之间的关系(BMP)连接调控信号和差距细胞间的沟通,我们检查了影响BMP-2和缝隙连接阻断剂18α甘草次酸(18 alpha-gca)间充质细胞凝结和chondrogenic在体外chondrogenic分化模型。明显与早期的间充质细胞的凝结和软骨形成高密度肢芽细胞培养。connexin43信使rna是最大限度地调节48 h治疗后与人类BMP-2重组相应的蛋白表达的变化。抑制连接调控细胞间的差距与2.5 microM 18 alpha-gca沟通chondrogenic分化减少了50%96 h对管家基因没有影响。暴露于18 alpha-gca只有第一个24 - 48电镀不影响凝结或后h后来chondrogenic分化建议这一差距连接调控细胞间沟通不是最初的关键冷凝但很重要的阶段出现分化。阻止chondrogenic BMP-2没有影响影响细胞数量或connexin43表达式。这些观察表明18 alpha-gca-sensitive细胞间的监管沟通在肢体间充质细胞接受chondrogenic分化和表明BMP-2诱导chondrogenic分化可能通过介导的connexin43表达式的调制和差距连接调控细胞间的沟通。

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