Effects of Histone Deacetylase Inhibitors (Valporic Acid, VPA) on Osteogenic Differentiation and Gene Expression of Human Dental Papilla Cells

Histones are responsible for the first level of DNA packing in eukaryotic chromatin.The organization of chromatin serves a dual purpose, one function is to pack the DNA into a compact form inside the nucleus of a cell, and the other is regulatory. Epigenetic modifications of chromatin play key roles in chromatin structure and the regulation of gene expression. Histone acetylation and deacetylation play a direct role in the regulation of gene transcription. Recently, histone deacetylase inhibitors (HDI) were shown to inhibit histone deacetylases ( HDACs), thus cause growth arrest and induce differentiation of transformed cells in culture and inhibit tumor growth in vivo. Normal cells also undergo cell cycle arrest and differentiation in the presence of HDI which means HDI had potential for applying on stem cells induction and tissue engineering. The dental papilla contributes to tooth formation and eventually converts to pulp tissue, so it had multipotent progenitor characteristic in different induction environment. There is evidence that the dental papilla cells were as potent in osteo/ dentinogenic differentiation and showed the osteoblastic phenotype.he purpose of this study was to examine the effect of Valporic acid, an histone deacetylase inhibitor, on the expression of osteogenic differentiation markers in the human dental papilla cells. The cells were cultured in standard medium or induction medium with osteogenic supplements including L-ascorbic acid 2-phosphate (0.05mM), sodium β- glycerophosphate (10 mM) and dexamethasone (10 -7 M).ur results demonstrated the progressive increase of ALP activity and extracellular matix mineralization in human dental papilla cells when cultured in induction medium. Theses results implied the osteoblastic phenotype of human dental papilla cells. The mRNA expression of ALP, OC, Cbfa-1 and COL-I was upregulated by VPA (1mM) in standard medium as well as induction medium, especially in short-term culture. Although the VPA in standard medium could upregulate the expression of osteoblastic marker genes, no significant extracellular matrix mineralization was noted. As to long-term culture, the upregulatory effect of VPA on osteoblastic marker genes progressively diminished in both standard and induction medium. The results of this study suggest that VPA can accelerate osteogenic differentiation of dental papilla cells. The expression of ALP activity and extracellular matrix mineralization in VPA-treated group was noted earlier than those in control group. However, in the long-term culture, the difference in the matrix mineralization did not reach statistically significant level.