Epigenetic Signals during Odontoblast Differentiation

Abstract

Odontoblast terminal differentiation occurs according to a tooth-specific pattern and implies both temporospatially regulated epigenetic signaling and the expression of specific competence. Differentiation of odontoblasts (withdrawal from the cell cycle, cytological polarization, and secretion of predentin/dentin) is controlled by the inner dental epithelium, and the basement membrane (BM) plays a major role both as a substrate and as a reservoir of paracrine molecules. Cytological differentiation implies changes in the organization of the cytoskeleton and is controlled by cytoskeleton-plasma membrane-extracellular matrix interactions. Fibronectin is re-distributed during odontoblast polarization and interacts with cell-surface molecules. A non-integrin 165-kDa fibronectin-binding protein, transiently expressed by odontoblasts, is involved in microfilament reorganization. Growth factors (TGF beta 1, 2, 3/BMP2, 4, and 6), expressed in tooth germs, signal differentiation. Systemically derived molecules (IGF1) may also intervene. IGF1 stimulates cytological but not functional differentiation of odontoblasts: The two events can thus be separated. Immobilized TGF beta 1 (combined with heparin) induced odontoblast differentiation. Only immobilized TGF beta 1 and 3 or a combination of FGF1 and TGF beta 1 stimulated the differentiation of functional odontoblasts over extended areas and allowed for maintenance of gradients of differentiation. Presentation of active molecules in vitro appeared to be of major importance; the BM should fulfill this role in vivo by immobilizing and spatially presenting TGF beta s. Attempts are being made to investigate the mechanisms which spatially control the initiation of odontoblast differentiation and those which regulate its propagation. Analysis of molar development suggested that odontoblast differentiation and crown morphogenesis are interdependent, although the possibility of co-regulation requires further investigation.

Dynamic expression of Wnt signaling-related Dickkopf1, -2, and -3 mRNAs in the developing mouse tooth

“…The differentiation of amelo-and odontoblasts and subsequent dentin and enamel formation is regulated by epithelial-mesenchymal interactions between the dental papilla and inner dental epithelium cells and involves the activity of signaling molecules (for review, see Lesot et al, 2001). We found that in addition to being expressed in the developing mandibular bone, Dkk1 was prominently up-regulated in the preodontoblasts and the expression continued in the secretory odontoblasts.…”

Mouse tooth development time sequence determination for the ICR/Jcl strain

“…The different induction stages that precede the morphogenesis and differentiation of the teeth result from reciprocal interactions among stomodeal epithelial cells and mesenchymal cells derived from neural crests (ectomesenchyme) (12,13). The identification of numerous growth differentiation factors (14)(15)(16)(17), transcription factors (18)(19)(20)(21) and molecules of adhesion (22)(23)(24) expressed in the course of the development of the tooth have revealed associations of multiple genes with tooth morphogenesis. Studies on the functions of signals and tissue interactions in cultured tissue explants and in mutant mouse embryos have revealed inductive signaling and hierarchies in downstream transcription factors (25).…”

TGF-β Signal Transduction in Oro-facial Health and Non-malignant Disease (Part I)

“…These findings have subsequently been extended, and it has been postulated that TGF-␤s (TGF-␤1 and -␤3), derived from the enamel organ and immobilized and activated by components of the basement membrane, induce odontoblast differentiation. Odontoblasts, in turn, then express TGF-␤, which acts in an autocrine manner to stimulate the secretion of predentin and dentin (Lesot et al, 2001). This proposal is consistent with observations showing the presence of TGF-␤ isoforms in dentin matrices (Cassidy et al, 1997) and both TGF-␤ isoforms and T␤R-I and T␤R-II in odontoblasts (Sloan et al, 1999(Sloan et al, , 2000.…”