NOD2 is involved in regulating odontogenic differentiation of DPSCs suppressed by MDP through NF-κB/p65 signaling.

Dental pulp stem cells (DPSCs) are well known for their capable of both self-renewal and multilineage differentiation. Dental tissue diseases, include caries, are often accompanied by inflammatory microenvironment, and muramyl dipeptide (MDP) is involved in the inflammatory stimuli to influence the differentiation of DPSCs. Nucleotide-binding oligomerization domain 2 (NOD2), a member of the cytosolic Nod-like receptor (NLR) family, plays a key role in inflammatory homeostasis regulation, but the role of NOD2 in DPSCs differentiation under inflammatory is still unclear. In this study, we identified that MDP suppressed odontogenic differentiation of DPSCs via NOD2/ NF-κB/p65 signaling pathway. Alizarin red staining and ALP activity showed the odontogenic differentiation was suppressed by MDP in a concentration-dependent manner, and the expression of dentin differentiation marker protein dentin matrix protein 1 (DMP-1) and dentin Sialophosphoprotein (DSPP) also indicated the same results. The expression of NOD2 increased gradually with the concentration of MDP as well as the phosphorylation and nuclear translocation of p65, which meant NF-κB signaling pathway was activated. Further, the interference of NOD2 inhibited the phosphorylation and nuclear translocation of p65 and reversed the MDP-mediated decrease of odontoblast differentiation of DPSCs. Our study showed that MDP can inhibit the odontoblast differentiation of DPSCs in a concentration-dependent manner. The NF-κB signaling pathway was activated by increasing expression of NOD2. Interference of NOD2 reversed the negative ability odontoblast differentiation of DPSCs in the inflammatory environment. Our study might provide a theoretical basis for the clinical treatment for dentinogenesis of DPSCs.

General Control Nonrepressed Protein 5 Modulates Odontogenic Differentiation Through NF-κB Pathway in Tumor Necrosis Factor-α-Mediated Impaired Human Dental Pulp Stem Cells.

Dental pulp stem cells (DPSCs) from pulpitis patients showed defective osteogenic differentiation. However, as the most well-studied histone acetyltransferase, the impaired general control nonrepressed protein 5 (GCN5) plays essential roles in various developmental processes. The aim of this study was to investigate the effect of GCN5 on DPSCs odontogenic differentiation. The healthy dental pulp tissues were obtained from the extracted impacted third molar of patients with the informed consent. DPSCs were treated with a high concentration of tumor necrosis factor-alpha (TNF-α) (100 ng/mL) and odontogenic differentiation-related gene and GCN5 protein level by Western blot analysis. Proliferation of the DPSCs was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Immunofluorescence staining detected GCN5 and NF-κB signaling for p-p65. The mechanism of GCN5 regulating odontogenic differentiation of DPSCs was determined by small interfering RNA analysis. Our data suggested that TNF-α can significantly reduce mineralization and the expression of dentin matrix acidic phosphoprotein 1 and dentin sialophosphoprotein at higher concentration (100 ng/mL). Meanwhile, it showed that the inflammation in microenvironment resulted in a downregulation of GCN5 expression and GCN5 knockdown caused decreased odontogenic differentiation of DPSCs was also found. In addition, the knockdown of GCN5 increased the expression of phosphorylation of p65, thus activating NF-κB pathway of DPSCs. Meanwhile, NF-κB pathway inhibitor pyrrolidinedithiocarbamic acid reversed the siGCN5 decreased odontogenic differentiation of DPSCs. Altogether, our findings indicated that in inflammatory microenvironments GCN5 plays a protective role in pulpitis impaired odontogenic differentiation of DPSCs by activating NF-κB pathway, which may provide a potential approach to dentin regeneration.

Palladium-catalyzed oxidative C-H/C-H cross-coupling of 1-substituted 1,2,3-triazoles with furans and thiophenes.

Palladium-catalyzed heteroarylation of 1-substituted 1,2,3-triazoles with furans and thiophenes has been developed in the presence of pyridine and Ag2CO3. The procedure is suitable for the regioselective preparation of 1,5-disubstituted 1,2,3-triazoles through conventional heating at reaction temperatures of 90-100 °C for 18 h.

Palladium-catalyzed ortho-alkoxylation of 2-aryl-1,2,3-triazoles.

Palladium-catalyzed alkoxylation of 2-aryl-1,2,3-triazoles was described in the presence of various groups in the aromatic rings. In addition, some other directing groups of heterocycles containing nitrogen were explored.

An easy arylation of 2-substituted 1,2,3-triazoles.

A selective, efficient and catalytic ligand-free method for the direct arylation of 2-aryl-1,2,3-triazoles via Pd-catalyzed C-H bond activation is described. The process smoothly proceeds in moderate to excellent yields.

Regioselective halogenation of 2-substituted-1,2,3-triazoles via sp2 C-H activation.

A highly regioselective halogenation of 2-substituted-1,2,3-triazoles was developed via sp(2) C-H activation. This method is compatible with halogen atoms, as well as electron-donating and electron-withdrawing groups. Meanwhile, the strategy is also efficient for the synthesis of a key intermediate of Suvorexant.

A novel and universal route to SiO2-supported organic/inorganic hybrid noble metal nanomaterials via surface RAFT polymerization.

Polymer-encapsulated gold or silver nanoparticles were synthesized and sterically stabilized by a shell layer of poly(4-vinylpyridine) (P4VP) grafted on SiO(2) nanoparticles that acts as a scaffold for the synthesis of hybrid noble metal nanomaterials. The grafting P4VP shell was synthesized via surface reversible addition-fragmentation chain transfer (RAFT) polymerization of 4-vinylpyridine (4VP) using SiO(2)-supported benzyl 9H-carbazole-9-carbodithioate (SiO(2)-BCBD) as the RAFT agent. The covalently tethered P4VP shell can coordinate with various transition metal ions such as Au(3+) or Ag(+) and therefore stabilize the corresponding Au or Ag nanoparticles reduced in situ by sodium borohydride (NaBH(4)) or trisodium citrate. The SiO(2)-supported RAFT agent and the Au or Ag nanoparticles embedded in the P4VP shell layer were characterized by UV-vis spectrophotometer, X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and surface-enhanced Raman spectroscopy (SERS).