Thesleff I, Vaahtokari A
Department of Pedodontics and Orthodontics, University of Helsinki, Finland.
Proc Finn Dent Soc. 1992;88 Suppl 1:357-68.
In developing teeth the differentiation of odontoblasts is triggered by the enamel epithelium and is tightly coupled with morphogenesis. There is substantial evidence that even in mature teeth the cells of the dental pulp retain the capability to differentiate into odontoblasts under suitable conditions. However, cells from other than the dental mesenchymal cell lineage apparently do not possess this potential. Thus, it is conceivable that the dental mesenchymal cells acquire cell type-specific potential to differentiate into odontoblasts during their developmental history. Therefore, the understanding of the mechanisms which regulate the terminal differentiation of odontoblasts requires that the molecular changes and mechanisms that are associated with their progressive determination be clarified. It can be speculated that there are key transition points in the developmental sequence during which the mesenchymal cells acquire new levels of differentiation. These include, (1) the condensation of the neural crest-derived mesenchymal cells around the epithelial bud, (2) their entrance into the dental papilla lineage during cap stage, and (3) the differentiation of the cells underlying the enamel epithelium into odontoblasts during bell stage. The transition points are conceivably characterized by amplification or onset of expression of new sets of genes encoding transcription factors, growth factors as well as structural proteins. We have applied in situ hybridization for localization of the expression of two growth factors during mouse molar morphogenesis: transforming growth factor beta 1 (TGF beta 1) and int-2 (a proto-oncogene coding for a fibroblast growth factor-related protein). During bud stage, expression of TGF beta 1 was first detected in the epithelium and shortly thereafter in the condensed dental mesenchyme. The expression was weak during early bell stage but a high number of transcripts appeared in secretory odontoblasts as well as in presecretory ameloblasts. int-2 mRNA appeared in the dental papilla mesenchyme at the onset of cap stage, persisted in the cuspal mesenchyme during bell stage and was lost upon completion of morphogenesis. Our findings suggest that cell type-specific expression of TGF beta 1 and int-2 is associated with phenotypic properties of the odontoblastic cell lineage. For instance, TGF beta 1 may regulate matrix deposition by increasing tenascin and syndecan expression in the condensed dental mesenchyme and by controlling dentin matrix deposition by odontoblasts. TGF beta 1 and int-2 may also be involved in signalling between the epithelial and mesenchymal tissues and in regulation of gene expression at the transition points of the developmental sequence that leads to the differentiation of odontoblasts.
在牙齿发育过程中，成牙本质细胞的分化由釉质上皮触发，并与形态发生紧密相关。有大量证据表明，即使在成熟牙齿中，牙髓细胞在合适的条件下仍保留分化为成牙本质细胞的能力。然而，除牙间充质细胞系以外的细胞显然不具备这种潜能。因此，可以想象牙间充质细胞在其发育过程中获得了分化为成牙本质细胞的细胞类型特异性潜能。所以，要理解调控成牙本质细胞终末分化的机制，就需要阐明与其逐步确定相关的分子变化和机制。可以推测，在发育序列中有一些关键的转变点，在此期间间充质细胞获得了新的分化水平。这些包括：（1）神经嵴来源的间充质细胞围绕上皮芽的聚集；（2）帽状期它们进入牙乳头细胞系；（3）钟状期釉质上皮下方的细胞分化为成牙本质细胞。可以想象这些转变点的特征是编码转录因子、生长因子以及结构蛋白的新基因集的表达增加或开始表达。我们应用原位杂交技术定位了小鼠磨牙形态发生过程中两种生长因子的表达：转化生长因子β1（TGFβ1）和int-2（一种编码成纤维细胞生长因子相关蛋白的原癌基因）。在芽期，TGFβ1的表达首先在上皮中被检测到，随后不久在聚集的牙间充质中也被检测到。在钟状早期表达较弱，但在分泌期成牙本质细胞以及分泌前期成釉细胞中出现了大量转录本。int-2 mRNA在帽状期开始时出现在牙乳头间充质中，在钟状期持续存在于牙尖间充质中，并在形态发生完成后消失。我们的研究结果表明，TGFβ1和int-2的细胞类型特异性表达与成牙本质细胞系的表型特性相关。例如，TGFβ1可能通过增加聚集的牙间充质中腱生蛋白和多功能蛋白聚糖的表达以及控制成牙本质细胞的牙本质基质沉积来调节基质沉积。TGFβ1和int-2也可能参与上皮和间充质组织之间的信号传导以及在导致成牙本质细胞分化的发育序列转变点处的基因表达调控。
