Galler K M, Yasue A, Cavender A C, Bialek P, Karsenty G, D'Souza R N
Department of Biomedical Sciences, Texas A&M University Health Science Center, Baylor College of Dentistry, 3302 Gaston Avenue, Dallas, TX 75246, USA.
J Dent Res. 2007 Oct;86(10):951-5. doi: 10.1177/154405910708601007.
The molecular mechanisms that maintain the equilibrium of odontoblast progenitor cells in dental pulp are unknown. Here we tested whether homeostasis in dental pulp is modulated by Twist-1, a nuclear protein that partners with Runx2 during osteoblast differentiation. Our analysis of Twist-1(+/-) mice revealed phenotypic changes that involved an earlier onset of dentin matrix formation, increased alkaline phosphatase activity, and pulp stones within the pulp. RT-PCR analyses revealed Twist-1 expression in several adult organs, including pulp. Decreased levels of Twist-1 led to higher levels of type I collagen and Dspp gene expression in perivascular cells associated with the pulp stones. In mice heterozygous for both Twist-1 and Runx2 inactivation, the phenotype of pulp stones appeared completely rescued. These findings suggest that Twist-1 plays a key role in restraining odontoblast differentiation, thus maintaining homeostasis in dental pulp. Furthermore, Twist-1 functions in dental pulp are dependent on its interaction with Runx2.
维持牙髓中牙本质细胞祖细胞平衡的分子机制尚不清楚。在这里，我们测试了牙髓中的稳态是否受Twist-1调节，Twist-1是一种在成骨细胞分化过程中与Runx2相互作用的核蛋白。我们对Twist-1(+/-)小鼠的分析揭示了表型变化，包括牙本质基质形成提前、碱性磷酸酶活性增加以及牙髓内出现牙髓石。RT-PCR分析显示Twist-1在包括牙髓在内的多个成年器官中表达。Twist-1水平降低导致与牙髓石相关的血管周围细胞中I型胶原蛋白和Dspp基因表达水平升高。在Twist-1和Runx2均失活的杂合小鼠中，牙髓石的表型似乎完全得到挽救。这些发现表明，Twist-1在抑制成牙本质细胞分化中起关键作用，从而维持牙髓的稳态。此外，Twist-1在牙髓中的功能依赖于其与Runx2的相互作用。
