Department of Oral and Maxillofacial Surgery, University of Regensburg, Regensburg, Germany.
Stem Cells Dev. 2012 Jul 20;21(11):1936-47. doi: 10.1089/scd.2011.0422. Epub 2012 Feb 7.
The transcription factor DLX3 plays a decisive role in bone development of vertebrates. In neural-crest derived stem cells from the dental follicle (DFCs), DLX3 is differentially expressed during osteogenic differentiation, while other osteogenic transcription factors such as DLX5 or RUNX2 are not highly induced. DLX3 has therefore a decisive role in the differentiation of DFCs, but its actual biological effects and regulation are unknown. This study investigated the DLX3-regulated processes in DFCs. After DLX3 overexpression, DFCs acquired a spindle-like cell shape with reorganized actin filaments. Here, marker genes for cell morphology, proliferation, apoptosis, and osteogenic differentiation were significantly regulated as shown in a microarray analysis. Further experiments showed that DFCs viability is directly influenced by the expression of DLX3, for example, the amount of apoptotic cells was increased after DLX3 silencing. This transcription factor stimulates the osteogenic differentiation of DFCs and regulates the BMP/SMAD1-pathway. Interestingly, BMP2 did highly induce DLX3 and reverse the inhibitory effect of DLX3 silencing in osteogenic differentiation. However, after DLX3 overexpression in DFCs, a BMP2 supplementation did not improve the expression of DLX3 and the osteogenic differentiation. In conclusion, DLX3 influences cell viability and regulates osteogenic differentiation of DFCs via a BMP2-dependent pathway and a feedback control.
转录因子 DLX3 在脊椎动物的骨骼发育中起着决定性作用。在牙齿滤泡（DFC）中的神经嵴衍生的干细胞中，DLX3 在成骨分化过程中差异表达，而其他成骨转录因子如 DLX5 或 RUNX2 则没有被高度诱导。因此，DLX3 在 DFC 的分化中起着决定性的作用，但它的实际生物学效应和调控机制尚不清楚。本研究探讨了 DLX3 在 DFC 中的调控过程。在 DLX3 过表达后，DFC 获得了纺锤形细胞形状，肌动蛋白丝重新排列。在这里，细胞形态、增殖、凋亡和成骨分化的标记基因的表达显著受到调控，如微阵列分析所示。进一步的实验表明，DFC 的活力直接受到 DLX3 表达的影响，例如，DLX3 沉默后凋亡细胞的数量增加。这种转录因子刺激 DFC 的成骨分化，并调节 BMP/SMAD1 通路。有趣的是，BMP2 高度诱导 DLX3，并逆转成骨分化中 DLX3 沉默的抑制作用。然而，在 DFC 中转染 DLX3 后，BMP2 的补充并没有改善 DLX3 的表达和成骨分化。总之，DLX3 通过 BMP2 依赖性途径和反馈控制影响细胞活力，并调节 DFC 的成骨分化。
