PNAS：发现人类牙齿更新的分子机制

日前，加州大学洛杉矶分校与中国中南大学湘雅医院的科学家发现，美洲短吻鳄可能作为一个合适的模型用来研究成年人类的牙齿替换。多数脊椎动物在其一生当中都可以更新牙齿，但人类的牙齿只能自然替换一次，尽管称为牙板的对牙齿发育具有关键作用的一个上皮组织带持续存在。

为了发现牙齿更新的分子机制，研究人员研究了美洲短吻鳄重复性的牙齿形成。由于短吻鳄有排列良好的牙齿，其形态特征类似于哺乳动物的牙齿——诸如继发腭和牙骨在牙槽中的植入——而且终生有能力更新牙齿，研究人员推断，长寿命的短吻鳄——它们口中的80颗牙齿的每一颗最多可替换50次——可能作为哺乳动物牙齿替换的模型。通过把组织学、分子与成像技术结合起来，研究人员发现短吻鳄的每一颗牙都是由3个组成部分构成的复杂的单元，这3个组成部份处在不同的发育阶段，而这种构造的目的是为了在牙齿一旦脱落后促进其进行替换。

研究人员表示，在牙齿早期发育阶段，短吻鳄的牙板在其末端形成了突起，而该末端中含有被公认为是静态的干细胞。分子分析表明这种牙齿周期的开始与一系列涉及牙齿发育的信号传导分子的动态表达有关。

研究人员表示，这些发现可能有助于触发失去牙齿的成年人牙齿更新的举措或者抑制有额外牙齿的人们不受控制的牙齿发育。

与牙齿相关的拓展阅读：

• 牙齿缺失可预测类风湿性关节炎

Specialized stem cell niche enables repetitive renewal of alligator teeth

Abstract

Reptiles and fish have robust regenerative powers for tooth renewal. However, extant mammals can either renew their teeth one time (diphyodont dentition) or not at all (monophyodont dentition). Humans replace their milk teeth with permanent teeth and then lose their ability for tooth renewal. Here, we study tooth renewal in a crocodilian model, the American alligator, which has well-organized teeth similar to mammals but can still undergo life-long renewal. Each alligator tooth is a complex family unit composed of the functional tooth, successional tooth, and dental lamina. Using multiple mitotic labeling, we map putative stem cells to the distal enlarged bulge of the dental lamina that contains quiescent odontogenic progenitors that can be activated during physiological exfoliation or artificial extraction. Tooth cycle initiation correlates with β-catenin activation and soluble frizzled-related protein 1 disappearance in the bulge. The dermal niche adjacent to the dermal lamina dynamically expresses neural cell adhesion molecule, tenascin-C, and other molecules. Furthermore, in development, asymmetric β-catenin localization leads to the formation of a heterochronous and complex tooth family unit configuration. Understanding how these signaling molecules interact in tooth development in this model may help us to learn how to stimulate growth of adult teeth in mammals.