Periodontal tissue is a functional unit supporting and encasing teeth. Cementum attaches each tooth to alveolar bone by embedding periodontal ligament adjacent to the surface of the tooth. Restoring lost periodontium, the ultimate goal of regenerative periodontal therapy, requires functional and anatomical reconstruction of a multitude of tissues including cementum, periodontal ligament, alveolar bone and gingiva. Recently, many studies on periodontal regeneration have been carried out, focusing on the regeneration or new attachment of damaged periodontal tissues. A specific concern for the clinician has been the limited predictability of cementogenesis, which is considered a prerequisite for complete restoration of periodontal tissues. Periodontal tissue generated during root formation. Toward the end of tooth crown development, epithelial cells from the enamel organ grow apically and form the Hertwig’s epithelial root sheath (HERS), an epithelial double cell layer indispensable for root formation. In this way, epithelial-mesenchymal interactions continue until completion of root development. While the root grows apically, more coronally located portions of the HERS disintegrate. Fragments of this disintegration process constitute the epithelial cell rests of Malassez (ERM), which reside in the periodontal ligament throughout life. The periodontal ligament arises from the dental follicle, an ectomesenchymal tissue encasing the developing tooth. Disintegration of HERS exposes the dentin surface and makes it accessible to other cells, for example, dental follicle cells. This is the moment when cementoblast differentiation starts and cementum matrix begins to be deposited on the exposed dentin surface. Cementogenesis importance of being known in the recent establishment of the periodontium. For example, periodontal ligament of attachment disorder is teeth due to cementum aplasia of metabolic disturbances, and will be caused an infection by bacterium. From those studies, it was found that the interactive functions of several biocontrol factors in cementum matrix play important roles in the regeneration and development of periodontal ligaments. It is well known that dental follicle cells of ectomesenchymal origin are capable of forming cementum when properly stimulated. As to the nature of the cementum forming cells (cementoblasts), there is a widely accepted opinion that they represent a population of periodontal cells, although some authors suggest that epithelial cells may also contribute to the process of cementum formation. To date, origin and differentiation mechanisms of cementoblast progenitors are unclear, and this is true for development and regeneration. Cellular and molecular mechanisms, which regulate formation of periodontal tissues, including cementum, have not been fully understood. To understand how the cementum formation during periodontal regeneration and development, and to make its application more concrete in regeneration, it is necessary to understand the mechanism at a sophisticated molecular level and also consider the control factors of specific functions. Among the various signaling factors, Wnt has been known to play an important role in forming periodontal tissue during the root development. Recently, dental researchers have focused on the potential role of Wnt signaling during morphogenesis of periodontal tissues. And β-Catenin is a key player in mediating epithelial- mesenchymal interactions during cementogenesis. As such, the HERS cell layer is important for regulating the initiation of cementum formation by control β-Catenin signaling in the cervical region where root development begins. The proliferation and differentiation of the enamel epithelium is believed to play an important role in normal growth of root and cementum formation. β-Catenin demonstrated the possibility of the initiation of early cementum layer formation by the extracellular matrix secretion of epithelial rests after HERS fragmentation, which contributed to root development in epithelial- mesenchymal interaction signal pathways. Osterox (Osx) regulates cementum formation by inhibit β-Catenin signal, and Smad4 is thought to play a role in the formation of the cementum through selective induction when embedding periodontal ligament fibers. We performed a tissue-specific control for β-Catenin, which plays a key role in the Wnt signaling pathway, in osteocalcin expression in odontoblast and cementoblast, and then identified the role of β-Catenin, the signal factors of Osx and Smad4, and interaction of cementum formation and the maintenance of periodontal tissue. Emerging regenerative strategies are promising to cure the irreversible damages to dental tissues, but the success of these strategies is constrained by the lack of insight on the molecular cues of regeneration, while recent advancements on the molecular controls of development of dental tissues provided valuable clues for identifying potential regenerative cues. These results support the concept that, during root development, the secreted products of the HERS induce adjacent cells of the periodontal ligament to differentiate and produce new cementum. Cementum formation is a key factor in the successful regeneration of periodontal tissue. It is believed that success induction of cellular cementum, rather than the cementum formation by selective induction, is more desirable for the regeneration of periodontal tissue and restoring proper cementum function.