The Role Of CREB In The Odonto/Osteogenic Differentiation Of Stem Cells From The Apical Papilla

Introduction Stem cell biology and tissue engineering develop rapidly, which promote the progress of regenerative medicine. The object of regenerative medicine is to create functional, dynamic organization, and repair or replace damaged tissue. In the discipline of endodontics, stem cells from the apical papilla(SCAPs) are the focus. They exist in periapical tissues of immature permanent teeth, having a high capacity of proliferation and self-renewal. SCAPs are thought to be the source of the root odontoblasts, eventually form root dentin. SCAPs may partially explain why apexogenesis can occur in these infected immature permanent teeth.The cAMP-responsive element-binding protein(CREB) plays a role in promoting the biomineralization of mesenchymal stem cells(MSCs). As the downstream of this signaling pathway, CREB played a key role by attaching to the conserved sequence of c AMP response genes. In human molar cementoblast and odontoblast cell nucleus, the expression of CREB was significantly high, while after CREB was suppressed, endochondral bone formation in mice was reduced. Besides, transcription factor CREB binding sites on the target gene CRE exist in many of the mineralization related gene promoter regions, such as OCN and BSP. These findings suggest CREB plays an important role in the process of biomineralization. However, the role of CREB in the odonto/osteogenic differentiation of SCAPs remains unclear.Aim To investigate the role of CREB in the regulation of odonto/osteogenic differentiation of SCAPs.Methods SCAPs were obtained from human normal impacted third molars. After transduction CREB overexpressd/silenced lentivirus into SCAPs, the mineralized nodule formation, m RNA and protein expressions of mineralization-related genes were measured.Results The overexpression of CREB enhanced mineralization nodule formation and up-regulated the m RNA levels of odonto/osteogenic-related markers, including alkaline phosphatase(ALP), collagen type I(Col I), runt-related transcription factor 2(RUNX2), osterix(OSX), and osteocalcin(OCN), as well as dentin sialoprotein protein(DSP) levels. In contrast, the silencing of CREB inhibited the mineralization capacity of the SCAPs and decreased the expression of odonto/osteogenic-related markers.Conclusion Our results indicate that the up-regulation of CREB expression may promote odonto/osteogenic differentiation of SCAPs in vitro and suggest a potential target gene for promoting dental tissue regeneration.