Mineral Trioxide Aggregate Promotes the Odonto/Osteogenic Differentiation and Dentinogenesis of Stem Cells from Apical Papilla via Nuclear Factor Kappa B Signaling Pathway

Introduction: Mineral trioxide aggregate (MTA) has been widely used in clinical apexification and apexogenesis. However, the effects of MTA on the stem cells from apical papilla (SCAPs) and the precise mechanism of apexogenesis have not been elucidated in detail. Methods: Multiple colony-derived stem cells were isolated from the apical papillae, and the effects of MTA on the proliferation and differentiation of SCAPs were investigated both in vitro and in vivo. Activation of nuclear factor kappa B (NF kappa B) pathway in MTA-treated SCAPs was analyzed by immunofluorescence assay and Western blot. Results: MTA at the concentration of 2 mg/mL did not affect the proliferation activity of SCAPs. However, 2 mg/mL MTA-treated SCAPs presented the ultrastructural changes, up-regulated alkaline phosphatase, increased calcium deposition, up-regulated expression of odontoblast markers (dentin sialoprotein and dentin sialophosphoprotein) and odonto/osteoblast markers (runt-related transcription factor 2 and osteocalcin), suggesting that MTA enhanced the odonto/osteoblastic differentiation of SCAPs in vitro. In vivo results confirmed that MTA can promote the regular dentinogenesis of SCAPs. Moreover, MTA-treated SCAPs exhibited the upregulated cytoplasmic phos-I kappa B alpha and phos-P65, enhanced nuclear P65, and increased nuclear translocaton of P65. When co-treated with BMS345541 (the specific NF kappa B inhibitor), MTA-mediated odonto/osteoblastic differentiation was significantly attenuated. Conclusions: MTA at the concentration of 2 mg/mL can improve the odonto/osteogenic capacity of SCAPs via the activation of NF kappa B pathway.