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Abstract：
To investigate the cell linkage between tooth dentin and bones, we studied TGF-β roles during postnatal dentin development using TGF-β receptor 2 (Tgfβr2) cKO models and cell lineage tracing approaches. Micro-CT showed that the early Tgfβr2 cKO exhibit short roots and thin root dentin (n = 4; p<0.01), a switch from multilayer pre-odontoblasts/odontoblasts to a single-layer of bone-like cells with a significant loss of ~85% of dentinal tubules (n = 4; p<0.01), and a matrix shift from dentin to bone. Mechanistic studies revealed a statistically significant decrease in odontogenic markers, and a sharp increase in bone markers. The late Tgfβr2 cKO teeth displayed losses of odontoblast polarity, a significant reduction in crown dentin volume, and the onset of massive bone-like structures in the crown pulp with high expression levels of bone markers and low levels of dentin markers. We thus concluded that bones and tooth dentin are in the same evolutionary linkage in which TGF-β signaling defines the odontogenic fate of dental mesenchymal cells and odontoblasts. This finding also raises the possibility of switching the pulp odontogenic to the osteogenic feature of pulp cells via a local manipulation of gene programs in future treatment of tooth fractures.
摘要：
为了研究牙齿牙本质和骨骼之间的细胞联系，我们使用TGF-β受体2（Tgfβr2）cKO模型和细胞谱系追踪方法研究了TGF-β在出生后牙本质发育过程中的作用。Micro-CT显示早期Tgfβr2cKO表现为短根和细根牙本质（n=4；p<0.01），从多层成牙本质细胞/成牙本质细胞转变为单层骨样细胞，牙本质小管的显着损失约为85％（n=4；p<0.01），从牙本质到骨骼的基质转移。机制研究显示牙源性标志物的统计学显着下降，骨骼标记物急剧增加。晚期Tgfβr2cKO牙齿显示成牙本质细胞极性丧失，牙冠牙本质体积显著减少，以及冠髓中大量骨样结构的出现，其中骨标志物的表达水平高，牙本质标志物的表达水平低。因此，我们得出结论，骨骼和牙齿牙本质处于相同的进化联系，其中TGF-β信号传导定义了牙间充质细胞和成牙本质细胞的牙源性命运。这一发现还提高了在未来的牙齿骨折治疗中通过基因程序的局部操纵将牙髓牙源性转换为牙髓细胞的成骨特征的可能性。
