Tubular Dentin Regeneration and Its Clinical Application

Abstract: A healthy tooth is composed of nearly 70% dentin enclosing the entire dental pulp, which is a pool of diverse stem cells. Loss of dentin not only generates unpleasant pain but also ultimately leads to the weakening of whole tooth stability due to reduced dentin thickness. Regenerative dental medicine has rapidly progressed since the advancement of stem cell biology and material science. However, more emphasis has been placed on the success of tissue formation than on how well the newly generated tissue retains the original organ structure and function. Based on the knowledge that epithelial-mesenchymal interaction is essential for tooth development, we previously discovered a dental epithelium-derived protein called Copine 7 (CPNE7). CPNE7 is an evolutionarily conserved, calcium-dependent phospholipid-binding protein and consists of two C2 domains in the N terminus and a von Willebrand factor A domain in the C terminus. Secreted from pre-ameloblasts, CPNE7 induces odontoblast differentiation in vitro and promotes dentin formation ex vivo. As a result, CPNE7 was suggested as a new molecule with the potential to diffuse across the dentin and induce tertiary dentinogenesis. The fact that recombinant CPNE7 is a cell-derived soluble bioactive molecule makes it a promising candidate for use in regenerative dental medicine. Moreover, a synthetic CPNE7-derived oligopeptide, Cpne7-DP, was developed which induces odontoblast differentiation in vitro and physiologic dentin formation in vivo. Comprehensive evaluation of Cpne7-DP further validated its potential as a bioactive therapeutic agent. Our results suggest that the dual functions of Cpne7-DP in tubular dentin formation and peritubular space occlusion are promising for oral disease-targeted application, especially those involving dentinal loss and sensitivity.