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.