TWIST1 promotes the odontoblast-like differentiation of dental stem cells.
TWIST1 promotes the odontoblast-like differentiation of dental stem cells.
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DOI：
10.1177/0022034511405387
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发表时间：
2011-07-01
影响因子：
--
通讯作者：
D'Souza, R N
中科院分区：
文献类型：
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作者：
Li, Y;Lu, Y;D'Souza, R N
当提供适当的条件时，从拔出的人第三磨牙（DPSC）的牙髓中提取的干细胞有可能分化成成牙本质细胞、成骨细胞、脂肪细胞和神经细胞。为了推进 DPSC 在牙本质再生中的应用，复制驱动牙齿发育过程中成牙本质细胞分化终末事件的许可信号非常重要。这种策略可能会恢复更类似于原发牙本质管状性质的牙本质基质。由于培养条件的限制，利用离体基因治疗来驱动矿化细胞的终末分化具有广阔的前景。在这些研究中，我们询问 DPSC 中 TWIST1 的强制表达是否可以改变这些细胞分化为成牙本质细胞样细胞的潜力。由于 Runx2 和 Twist1 蛋白之间的伙伴关系已知可控制成骨细胞终末分化的开始，因此我们假设这些基因可控制 DPSC 的谱系决定。我们的结果首次表明，DPSC 中 Twist1 的过表达增强了 DSPP 的表达，DSPP 是一种标记成牙本质细胞终末分化的基因。此外，共转染测定表明，Twist1 通过拮抗 293FT 细胞中的 Runx2 功能来刺激 Dspp 启动子活性。对我们体外数据的分析表明，DPSC 的谱系规范可以通过离体基因修饰来调节。
Stem cells derived from the dental pulp of extracted human third molars (DPSCs) have the potential to differentiate into odontoblasts, osteoblasts, adipocytes, and neural cells when provided with the appropriate conditions. To advance the use of DPSCs for dentin regeneration, it is important to replicate the permissive signals that drive terminal events in odontoblast differentiation during tooth development. Such a strategy is likely to restore a dentin matrix that more resembles the tubular nature of primary dentin. Due to the limitations of culture conditions, the use of ex vivo gene therapy to drive the terminal differentiation of mineralizing cells holds considerable promise. In these studies, we asked whether the forced expression of TWIST1 in DPSCs could alter the potential of these cells to differentiate into odontoblast-like cells. Since the partnership between Runx2 and Twist1 proteins is known to control the onset of osteoblast terminal differentiation, we hypothesized that these genes act to control lineage determination of DPSCs. For the first time, our results showed that Twist1 overexpression in DPSCs enhanced the expression of DSPP, a gene that marks odontoblast terminal differentiation. Furthermore, co-transfection assays showed that Twist1 stimulates Dspp promoter activity by antagonizing Runx2 function in 293FT cells. Analysis of our in vitro data, taken together, suggests that lineage specification of DPSCs can be modulated through ex vivo gene modifications.