In developing teeth, the sequential and reciprocal interactions between epithelial and mesenchymal tissues promote stem/progenitor cell differentiation. However, the origin of the stem/progenitor cells has been the subject of considerable debate. According to recent studies, mesenchymal stem cells originate from periarterial cells and are regulated by neurons in various organs. The present study examined the role of innervation in tooth development and rodent incisor stem/progenitor cell homeostasis. Rodent incisors continuously grow throughout their lives, and the lower incisors are innervated by the inferior alveolar nerve (IAN). In this study, we resected the IAN in adult rats, and the intact contralateral side served as a nonsurgical control. Sham control rats received the same treatment as the resected rats, except for the resection process. The extent of incisor eruption was measured, and both mesenchymal and epithelial stem/progenitor cells were visualized and compared between the IAN-resected and sham-operated groups. One week after surgery, the IAN-resected incisors exhibited a chalky consistency, and the eruption rate was decreased. Micro-computed tomography and histological analyses performed 4 wk after surgery revealed osteodentin formation, disorganized ameloblast layers, and reduced enamel thickness in the IAN-resected incisors. Immunohistochemical analysis revealed a reduction in the CD90- and LRIG1-positive mesenchymal cell ratio in the IAN-resected incisors. However, the p40-positive epithelial stem/progenitor cell ratio was comparable between the 2 groups. Thus, mesenchymal stem/progenitor cell homeostasis is more related to IAN innervation than to epithelial stem/progenitor cells. Furthermore, sensory nerve innervation influences subsequent incisor growth and formation.
Keywords: epithelial-mesenchymal interactions; mesenchymal stem cell; odontogenesis; progenitor cell; rat; stem cell niche.