Advances in defining regulators of cementum development and periodontal regeneration.

Substantial advancements have been made in defining the cells and molecular signals that guide tooth crown morphogenesis and development. As a result, very encouraging progress has been made in regenerating crown tissues by using dental stem cells and recombining epithelial and mesenchymal tissues of specific developmental ages. To date, attempts to regenerate a complete tooth, including the critical periodontal tissues of the tooth root, have not been successful. This may be in part due to a lesser degree of understanding of the events leading to the initiation and development of root and periodontal tissues. Controversies still exist regarding the formation of periodontal tissues, including the origins and contributions of cells, the cues that direct root development, and the potential of these factors to direct regeneration of periodontal tissues when they are lost to disease. In recent years, great strides have been made in beginning to identify and characterize factors contributing to formation of the root and surrounding tissues, that is, cementum, periodontal ligament, and alveolar bone. This review focuses on the most exciting and important developments over the last 5 years toward defining the regulators of tooth root and periodontal tissue development, with special focus on cementogenesis and the potential for applying this knowledge toward developing regenerative therapies. Cells, genes, and proteins regulating root development are reviewed in a question-answer format in order to highlight areas of progress as well as areas of remaining uncertainty that warrant further study.

Amelogenins regulate expression of genes associated with cementoblasts in vitro.

Amelogenins are major proteins expressed by ameloblasts during development of the crown (enamel and dentin). These matrix proteins guide crystal habits of the mineral phase of developing enamel and are possible regulators of other genes/proteins during development and maturation of crown and root (dentin and cementum). This study focused on defining the effect that a specific proteolytic cleavage product of amelogenin, tyrosine-rich amelogenin peptide (TRAP), has on cementoblast behavior. Immortalized cementoblasts (OCCM-30) were exposed to TRAP in vitro. Cells treated with TRAP were evaluated for cell proliferation, gene expression for osteocalcin (OCN), osteopontin (OPN), and bone sialoprotein (BSP), and induction of mineral nodule formation. No significant difference in cell proliferation was found between vehicle-treated cells and those treated with TRAP for up to 9 d after treatment. Gene expression of OCN, OPN, and BSP in TRAP-treated cementoblasts showed down-regulation, up-regulation, and no significant change, respectively, relative to vehicle control. A marked decrease in mineral nodule formation was found in cells treated with TRAP compared with the vehicle control, in a dose-dependent manner. These data, along with our previous results demonstrating similar activity with full-length amelogenin and leucine-rich amelogenin peptide (LRAP), suggest that amelogenin-like molecules regulate mesenchymal cell behavior.

The crowning achievement: getting to the root of the problem.

An ideal goal of oral-craniofacial dental reconstructive therapy is to establish treatment modalities that predictably restore functional tissues. One major area of focus has been in the area of dental materials with marked improvements in the design of materials used to restore teeth/periodontium/bone lost as a consequence of disease or disorders. With advances in understanding the cell and molecular controls for development and regeneration of tooth structures, it is now possible to consider therapies that promote regeneration of lost tissues, along with replacement of these tissues. This review presents a background on our current knowledge as to the composition of the tooth/periodontium followed by a discussion on successes to date, both in vitro and in vivo, toward regenerating a whole tooth and next steps required to regenerate a functional tooth.