EXPERIMENTAL INDUCTION OF ODONTOBLAST DIFFERENTIATION AND STIMULATIONDURING REPARATIVE PROCESSES

In vivo implantation experiments have shown that ethylenediaminetetraa cetic acid(EDTA)-soluble fractions of dentin stimulate reparative dent inogenesis. When isolated embryonic dental papillae were cultured in t he presence of these dentin constituents, odontoblast cytological and functional differentiation could be initiated and maintained in the ab sence of an enamel organ. These effects were attributed to the presenc e of TGF-beta-related molecules [TGF-beta1 or bone morphogenetic prote in-2a (BMP-2a)] which had to be used in combination with an EDTA-solub le fraction of dentin in order to specifically affect competent preodo ntoblasts. These EDTA-soluble constituents present in dentin could be replaced by heparin or fibronectin which both have been reported to in teract with TGF-beta. The association of such defined matrix component s with a TGF-beta-related molecule represents a biologically active co mplex triggering odontoblast functional differentiation. In response t o caries, odontoblasts modulate their secretory activity and are stimu lated to elaborate reactionary dentin. This might be induced by active molecules such as IGF, TGF-beta or BMP which are liberated from denti n consecutively to the demineralization process. Reparative dentinogen esis is distinct from reactionary dentinogenesis and more complex sinc e it implicates the differentiation of precursor cells present in the dental papilla. The developmental history of these cells is different from that of the physiological predontoblasts in developing teeth. The nature of these ''stem cells'' and the mechanism of their induction s till remain open questions.