HDAC Inhibitor Trichostatin A Promotes Proliferation and Odontoblast Differentiation of Human Dental Pulp Stem Cells

Abstract

Trichostatin A (TSA) is a potent histone deacetylase (HDAC) inhibitor with a broad spectrum of epigenetic activities known to regulate diverse cellular mechanisms, including differentiation of mesenchymal stem cells. In this study, we demonstrate that TSA promotes proliferation and odontoblast differentiation of human dental pulp stem cells (hDPSCs) in vitro and has the ability to enhance dentin formation and odontoblast differentiation in vivo during tooth development. We observed that TSA increased the expression of proliferating cell nuclear antigen and cyclin D1 in hDPSCs at a certain concentration and the activation of JNK/c-Jun pathway was essential for TSA-dependent hDPSC proliferation. Further, TSA accelerated mineral nodule formation in vitro and increased gene expression of dentin sialophosphoprotein, dentin matrix protein 1, bone sialoprotein, and osteocalcin. In addition, TSA significantly upregulated the levels of phospho-Smad2/3, Smad4, and nuclear factor I-C, while the specific inhibitor of Smad3 inhibits TSA enhancing mineralization differentiation of hDPSCs. HDAC3 is downregulated by TSA treatment, suggesting a possible mediator of TSA-dependent pathways among the members of HDAC family. Moreover, TSA-injected embryos exhibited increased dentin thickness, larger dentin areas, and higher odontoblast numbers in their postnatal molars with stronger dentin sialoprotein expression in immunohistochemical staining. These findings indicate that TSA may serve a key role in proliferation and odontoblast differentiation of hDPSCs in dental developmental stages and can be used as an accelerator in dental hard tissue engineering.

LBH589 Promotes Osteogenic and Dentinogenic Differentiation of Stem Cells from the Apical Papilla by Inhibiting Histone Deacetylation

“…showed that an HDAC inhibitor had the same effects on SCAPs as those reported by Jin et al on DPSCs 13) .…”

“…As a global inhibitor of histone deacetylases, trichostatin A (TSA) has been shown to elevate the transcriptional activity of runx2 and, consequently, to initiate downstream gene transcription, eventually promoting osteoblast progenitor differentiation by inhibiting the activation of histone deacetylase 6. Jin et al reported that the histone deacetylase inhibitor TSA enhanced the efficiency of odontoblast differentiation in dental pulp stem cells (DPSCs) 13) .…”

Inhibition of Histone Deacetylases Potentiates BMP9-Induced Osteogenic Signaling in Mouse Mesenchymal Stem Cells

“…Furthermore, VPA treatment led to an increased expression of osterix, osteopontin, BMP2, and Runx2 in human adipose tissue-derived stromal cells and bone marrow stromal cells [52]. Interestingly, TSA was shown to promote odontoblast differentiation of human dental pulp stem cells (hDPSCs) in vitro, and to enhance dentin formation and odontoblast differentiation in vivo during tooth development [53]. It is noteworthy that Hdacs inhibitors may achieve their promoting effects on osteogenic differentiation by inhibiting osteoclastogenesis [54,55,56].…”

Effects of washed platelets vs platelet-rich plasma on the proliferation and mineralization of rat dental pulp cells

“…Dental pulp cells cultured in vitro are able to form mineralization nodules at the site where cellular nodules exhibit multilayer growth and can aggregate under the effect of mineralization induction solution (Laiteerapong et al, 2012). Some studies have discovered that these mineralized nodules are primarily comprised of a dentin-like mineralized matrix, which has the characteristics of dentin (Jiang et al, 2012;Jin et al, 2013). Thus, at present, the formation of mineralized nodules is regarded as an important biological indicator of the detection of dentin generated in dental pulp cells (Du et al, 2013).…”