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Epigenetic Modulation for Reparative Dentinogenesis?
1 Department of Neuroscience and Biomedical Technologies, University of Milano-Bicocca, San Gerardo Hospital, via Donizetti 106-20052, Monza (MI), Italy; and Correspondence: * corresponding author, lucio.tremolizzo{at}unimib.it Several pieces of evidence have been reported supporting an important role played by epigenetic factors in the control of odontoblast differentiation (Ruch, 1998; Lesot et al., 2001). The term "epigenetic" generally encompasses all the complex gene-environment interactions responsible for phenotypic changes and, therefore, in our case, for the commitment toward the odontoblast terminal cell type. However, more specifically, the term epigenetic today refers to covalent modifications of DNA and histones responsible for changes in the degree of chromatin relaxation and the rate of gene transcription (Beck and Olek, 2003). Interestingly enough, one of the genes recently identified as characteristic of the odontoblast phenotype is reelin (Bleicher et al., 2001), an extracellular matrix protein highly expressed in the brain, for which a role in dentin-pulp complex innervation has been suggested. It is noteworthy that reelin expression is controlled by an epigenetic mechanism, i.e., cytosine methylation of the CpG island embedded in the promoter of the gene (Chen et al., 2002). Moreover, valproate, an anti-epileptic and mood-stabilizing drug, increases the levels of reelin mRNA in mouse brain via histone hyperacetylation and consequent chromatin relaxation (Tremolizzo et al., 2002). In light of these data, one possible very interesting experiment would now be to study whether valproate, by changing the expression of reelin and/or other genes, may result in modification of the process of reparative dentinogenesis. In conclusion, we propose that this evidence might allow one to speculate about a novel epigenetic pharmacological approach able to modulate the process of odontoblast differentiation, innervation, and, hypothetically, the subsequent secretion of the organic components of predentin-dentin, with possible important implications for clinical practice. Received for publication October 23, 2003. Accepted for publication December 22, 2003. REFERENCES
Journal of Dental Research, Vol. 83, No. 3,
198 (2004)
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