[The pattern and regulatory mechanism of mammalian diphyodont tooth replacement]

Although the dental lamina of permanent teeth in human being has been developed as early as the embryo stage, the replacement of the deciduous teeth by permanent teeth does not take place untill the age of 6 to 12 years old. The molecular mechanism of the initiation of permanent teeth is still unclear. The rodent species are usually used for the tooth development research in the past. However, this animal model is not suitable for the tooth replacement study because of the absence of tooth replacement in rodents. After 10 years of efforts, our team has established the animal model of miniature pig for tooth replacement research. Using this model, we firstly defined the spatiotemporal pattern of teeth replacement. In the further mechanism research, results showed that the growing rate of the deciduous teeth was faster than that of the surrounding alveolar bone, and biomechanical stress inside mandible was generated due to the fast growth of deciduous teeth. The stress might up-regulate the signal of Runt-related transcription factor 2 (RUNX2)-Wnt pathway in the mesenchyme between the deciduous and permanent teeth, sustain the successional dental lamina at the resting stage and inhibit the development of permanent teeth. A similar expression pattern was also found in the mesenchyme between the deciduous and permanent teeth in human. Our findings demonstrated that the eruption of deciduous tooth released the stress inside mandible, thus induced the "Wnt translocation" from the mesenchyme into the epithelium of permanent counterpart and therefore initiated the development of permanent teeth. The underlying mechanism of the replacement of deciduous teeth by permanent teeth is the regulation of biomechanical stress throughout the initiation process. Based on the findings, we proposed the theory of "biomechanical stress regulation of the tooth replacement" . The replacement pattern and regulatory mechanism provide a scientific foundation for the organ development and regeneration by regulating the biomechanical stress and Wnt pathway in the future.