Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, People's Republic of China; State Key Laboratory of Proteomics, Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing, People's Republic of China.
Stem Cells. 2014 Nov;32(11):2939-48. doi: 10.1002/stem.1772.
In mouse, continuous growth of the postnatal incisor is coordinated by two populations of multipotent progenitor cells, the dental papilla mesenchymal cells and dental epithelial stem cells, residing at the proximal end of the incisor, yet the molecular mechanism underlying the cooperation between mesenchymal and epithelial cells is largely unknown. Here, transforming growth factor-β (TGF-β) type II receptor (Tgfbr2) was specifically deleted within the postnatal dental papilla mesenchyme. The Tgfbr2-deficient mice displayed malformed incisors with wavy mineralized structures at the labial side as a result of increased differentiation of dental epithelial stem cells. We found that mesenchymal Tgfbr2 disruption led to upregulated expression of Wnt5a and downregulated expression of Fgf3/10 in the mesenchyme, both of which synergistically enhanced Lrp5/6-β-catenin signaling in the cervical loop epithelium. In accord with these findings, mesenchyme-specific depletion of the Wnt transporter gene Wls abolished the aberrant mineralized structures caused by Tgfbr2 deletion. Thus, mesenchymal TGF-β signaling provides a unifying mechanism for the homeostasis of dental epithelial stem cells via a Wnt signaling-mediated mesenchymal-epithelial cell interaction.
在小鼠中，出生后切牙的持续生长由位于切牙近端的两个多能祖细胞群体协调，即牙髓间质细胞和牙上皮干细胞，但间质细胞和上皮细胞之间合作的分子机制在很大程度上尚不清楚。在这里，转化生长因子-β（TGF-β）Ⅱ型受体（Tgfbr2）在出生后牙髓间质中特异性缺失。Tgfbr2 缺陷型小鼠的切牙表现为畸形，唇侧有波浪状矿化结构，这是由于牙上皮干细胞分化增加所致。我们发现，间质 Tgfbr2 的缺失导致间质中 Wnt5a 的表达上调和 Fgf3/10 的表达下调，两者协同增强了颈环上皮细胞中的 Lrp5/6-β-catenin 信号。与这些发现一致的是，Wnt 转运蛋白基因 Wls 的间质特异性缺失消除了 Tgfbr2 缺失引起的异常矿化结构。因此，间质 TGF-β 信号通过 Wnt 信号介导的间质-上皮细胞相互作用，为牙上皮干细胞的稳态提供了一个统一的机制。
