Margarita Zeichner‐David

During tooth development, after the completion of crown formation, the apical mesenchyme forms the developing periodontium while the inner and outer enamel epithelia fuse below the level of the crown cervical margin to produce a bilayered epithelial sheath termed Hertwig's epithelial root sheath (HERS). The role of HERS cells in root formation is widely accepted; however, the precise function of these cells remains controversial. Functions suggested have ranged from structural (subdivide the dental ectomesenchymal tissues into dental papilla and dental follicle), regulators of timing of root development, inducers of mesenchymal cell differentiation into odontoblasts and cementoblasts, to cementoblast cell precursors. The characterization of the HERS phenotype has been hindered by the small amount of tissue present at a given time during root formation. In this study, we report the establishment of an immortal HERS-derived cell line that can be maintained in culture and then induced to differentiate in vitro. Characterization of the HERS phenotype using reverse transcriptase-polymerase chain reaction and Western blot immunostaining suggests that HERS cells initially synthesize and secrete some enamel-related proteins such as ameloblastin, and then these cells appear to change their morphology and produce a mineralized extracellular matrix resembling acellular cementum. These studies suggest that the acellular and cellular cementum are synthesized by two different types of cells, the first one by HERS-derived cementoblasts and the later by neural crest-derived cementoblasts.

The mammalian tooth forms by a series of reciprocal epithelial-mesenchymal interactions. Although several signaling pathways and transcription factors have been implicated in regulating molar crown development, relatively little is known about the regulation of root development. Four genes encoding nuclear factor I (NFI) transcription-replication proteins are present in the mouse genome: Nfia, Nfib, Nfic, and NFIX: In order to elucidate its physiological role(s), we disrupted the Nfic gene in mice. Heterozygous animals appear normal, whereas Nfic(-/-) mice have unique tooth pathologies: molars lacking roots, thin and brittle mandibular incisors, and weakened abnormal maxillary incisors. Feeding in Nfic(-/-) mice is impaired, resulting in severe runting and premature death of mice reared on standard laboratory chow. However, a soft-dough diet mitigates the feeding impairment and maintains viability. Although Nfic is expressed in many organ systems, including the developing tooth, the tooth root development defects were the prominent phenotype. Indeed, molar crown development is normal, and well-nourished Nfic(-/-) animals are fertile and can live as long as their wild-type littermates. The Nfic mutation is the first mutation described that affects primarily tooth root formation and should greatly aid our understanding of postnatal tooth development.

Destruction of the periodontium is normally associated with periodontal disease, although many other factors, such as trauma, aging, infections, orthodontic tooth movement and systemic and genetic diseases, can contribute to this process. Strategies (such as guided tissue regeneration) have been developed to guide and control regeneration using bioresorbable membranes and bone grafts. Although effective to a certain point, these strategies have the problem that they are not predictable and do not completely restore the architecture of the original periodontium. To achieve complete repair and regeneration it is necessary to recapitulate the developmental process with complete formation of cementum, bone and periodontal ligament fibers. Detailed knowledge of the biology of cementum is key for understanding how the periodontium functions, identifying pathological issues and for developing successful therapies for repair and regeneration of damaged periodontal tissue. It is the purpose of this review to focus on the role of cementum and its specific components in the formation, repair and regeneration of the periodontium. As cementum is a matrix rich in growth factors that could influence the activities of various periodontal cell types, this review will examine the characteristics of cementum, its composition and the role of cementum components, especially the cementum protein-1, during the process of cementogenesis, and their potential usefulness for regeneration of the periodontal structures in a predictable therapeutic manner.