Kaushik Mukherjee1, Gayathri Visakan1, Jin-Ho Phark2, Janet Moradian-Oldak1. 1. Center for Craniofacial Molecular Biology, Division of Biomedical Sciences, Herman Ostrow School of Dentistry, University of Southern California, 2250 Alcazar Street, Los Angeles 90033, United States. 2. Herman Ostrow School of Dentistry, 925 W 34 St., University of Southern California, Los Angeles 90089, United States.
Abstract
Mammalian teeth primarily consist of two distinct calcified tissues, enamel and dentin, that are intricately integrated by a complex and critical structure, the dentin-enamel junction (DEJ). Loss of enamel exposes the underlying dentin, increasing the risk of several irreversible dental diseases. This paper highlights the significance of utilizing the functional domains of a major enamel matrix protein, amelogenin, intrinsic to tooth enamel and the DEJ interface, to rationally design smaller bioinspired peptides for regeneration of tooth microstructures. Using this strategy, we designed a synthetic peptide, P26, that demonstrates a remarkable dual mineralization potential to restore incipient enamel decay and mineralization defects localized in peripheral dentin below the DEJ. As a proof of principle, we demonstrate that interaction between P26 and collagen prompts peptide self-assembly, followed by mineralization of collagen fibrils in vitro. P26-mediated nucleation of hydroxyapatite (HAP) crystals on demineralized dentin in situ significantly facilitates the recovery of mineral density and effectively restores the biomechanical properties of dentin to near-native levels, suggesting that P26-based therapy has promising applications for treating diverse mineralized tissue defects in the tooth.
Mammalian teeth primarily consist of two distinct calcified tissues, enamel and dentin, that are intricately integpan class="Species">rated by a complex and critical structure, the dentin-enamel junction (DEJ). Loss of enamel exposes the underlying dentin, increasing the risk of several irreversible dental diseases. This paper highlights the significance of utilizing the functional domains of a major enamel matrix protein, amelogenin, intrinsic to tooth enamel and the DEJ interface, to rationally design smaller bioinspired peptides for regeneration of tooth microstructures. Using this strategy, we designed a synthetic peptide, P26, that demonstrates a remarkable dual mineralization potential to restore incipient enamel decay and mineralization defects localized in peripheral dentin below the DEJ. As a proof of principle, we demonstrate that interaction between P26 and collagen prompts peptide self-assembly, followed by mineralization of collagen fibrils in vitro. P26-mediated nucleation of hydroxyapatite (HAP) crystals on demineralized dentin in situ significantly facilitates the recovery of mineral density and effectively restores the biomechanical properties of dentin to near-native levels, suggesting that P26-based therapy has promising applications for treating diverse mineralized tissue defects in the tooth.
Authors: Yuanyuan Hu; Charles E Smith; Zhonghou Cai; Lorenza A-J Donnelly; Jie Yang; Jan C-C Hu; James P Simmer Journal: Mol Genet Genomic Med Date: 2016-10-05 Impact factor: 2.183
Authors: Ophir D Klein; Olivier Duverger; Wendy Shaw; Rodrigo S Lacruz; Derk Joester; Janet Moradian-Oldak; Megan K Pugach; J Timothy Wright; Sarah E Millar; Ashok B Kulkarni; John D Bartlett; Thomas Gh Diekwisch; Pamela DenBesten; James P Simmer Journal: Int J Oral Sci Date: 2017-11-22 Impact factor: 6.344