Histone deacetylase inhibition with valproic acid downregulates osteocalcin gene expression in human dental pulp stem cells and osteoblasts : evidence for HDAC2 involvement

摘要: Adult mesenchymal stem cells, such as dental pulp are of great interest for cell-based tissue engineering strategies because they can differentiate into a variety tissue-specific above all, osteoblasts. In recent years, epigenetic studies on cells have indicated that specific histone alterations and modifying enzymes play essential roles in cell differentiation. However, although several reported valproic acid (VPA)—a selective inhibitor deacetylases (HDAC)—enhances osteoblast differentiation, data osteocalcin expression—a late-stage marker differentiation—are limited. We therefore decided to study the effect VPA A low concentration did not reduce viability, proliferation, or cycle profile. it was sufficient significantly enhance matrix mineralization by increasing osteopontin bone sialoprotein expression. contrast, levels were decreased, an induced at transcriptional level, strongly correlated with inhibition HDAC2. fact, HDAC2 silencing shRNA produced similar treatment expression osteoblast-related markers. conclude does induce terminal differentiation osteoblasts, but stimulates generation less mature cells. Moreover, suppression individual HDAC RNA interference could only single aspect thus produce effects.