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Background: Stem cells from apical papilla (SCAP) located in the root apex of immature permanent teeth are a reliable cell source for pulp-dentine complex regeneration. Mineral trioxide aggregate (MTA) is a biocompatible material which has been widely used in endodontic treatments. The aim of this study was to elucidate the regulatory role of MTA in the proliferation and differentiation of SCAP. Methods: Cell viability was detected by Cell counting kit-8. Characteristics of SCAP were confirmed by Flow cytometric (FCM) analysis and alizarin red staining. Then, MTA-mediated osteo/odontogenic differentiation of SCAP was investigated by reverse transcription polymerase chain reaction. The effect of MAPKs on MTA-mediated osteo/ odontogenic differentiation was evaluated by western blot analysis.Results: There was no significant difference in cell viability between the control group and the group with lower concentrations of MTA. However, higher concentrations of MTA could inhibit proliferation of SCAP. It is demonstrated that the ALP activity were enhanced, the mRNA and protein expression of BSP, OCN, DSPP, Runx2 were up-regulated. In addition, phosphorylation proteins of ERK, p38 were activated through western blot analysis.Conclusions: MTA at appropriate concentration could enhance osteo/odontogenic differentiation of SCAP by activating p38 and ERK signaling pathways. This study provides a new idea for the clinical application of MTA and the treatment of endodontic diseases.

Osteo/odontogenic differentiation is a key process of human stem cells from apical papilla (SCAP) in tooth root development. Emerging evidence indicates microRNAs (miRNAs) play diverse roles in osteogenesis. However, their functions in osteo/odontogenic differentiation of SCAP require further elucidation. To investigate the role of miRNA in SCAP osteo/odontogenic differentiation and underlying mechanisms, miRNA microarray analysis was performed to screen differentially expressed miRNAs between control and osteo/odontogenic-induced group. Quantitative real-time PCR (qRT-PCR) and western blot were used to detected osteo/odontogenic differentiationrelated markers and possible signaling pathway SCAP-associated genes. Alizarin Red Staining (ARS) were applied to evaluated osteogenic capacity. The results showed that miR-497-5p increased during SCAP osteo/odontogenic differentiation. Overexpression of miR-497-5p enhanced the osteo/odontogenic differentiation of SCAP, whereas downregulation of miR-497-5p elicited the opposite effect, thus suggesting that miR-497-5p is a positive regulator of the osteo/odontogenic differentiation of SCAP. Bioinformatic analysis and dual luciferase reporter assay identified that SMAD specific E3 ubiquitin protein ligase 2 (Smurf2) is a direct target of miR-497-5p. Further study demonstrated that Smurf2 negatively regulates SCAP osteo/odontogenic differentiation, and silencing Smurf2 could block the inhibitory effect of the miR-497-5p inhibitor. Meanwhile, pathway detection manifested that miR-497-5p promotes osteo/odontogenic differentiation via Smad signaling pathway. Collectively, our findings demostrate that miR-497-5p promotes osteo/odontogenic differentiation of SCAP via Smad signaling pathway by targeting Smurf2.

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The theoretical calculations show that [60]fullerene-fused dihydrocarboline derivatives exhibit significant first hyperpolarizability contrasts induced by their electrochemical feature.

Layered sandwich metallacarboranes have various advantages including structural diversity, tailoring ability, rich electrochemical properties, and high thermal stability and thus could be potential multifunctional nonlinear optical (NLO) materials. In this study, second-order NLO properties and the multi-state switching effect of the layered cobaltacarborane, induced by electrochemical behavior, were explored using density functional theory (DFT). The calculated first hyperpolarizabilities (β) illustrated that the NLO responses are enhanced with the increasing of layers, which was mainly attributed to the C → B intraligand charge transfer (C 2 B 3 ) (ILCT) and metal-centered d → d transition (MCT) as indicated by the time-dependent (TD)DFT results. Remarkable β contrasts were observed after undergoing two sequential one-electron redox processes. Therefore, the pronounced multi-state NLO switch can be achieved. In mixed-valence systems, the metal−metal interaction plays a crucial role in the NLO responses through intervalence charge transfer (IVCT) and the π → π* transition of the whole metal−bridge−metal system.