The purpose of this study was to investigate the effects of mesoporous bioactive glass nanoparticle (MBN)/graphene oxide (GO) composites on the mineralization ability and differentiation potential of human dental pulp stem cells (hDPSCs). MBN/GO composites were synthesized using the sol-gel method and colloidal processing to enhance the bioactivity and mechanical properties of MBN. Characterization using FESEM, XRD, FTIR, and Raman spectrometry showed that the composites were successfully synthesized. hDPSCs were then cultured directly on the MBN/GO (40:1 and 20:1) composites in vitro. MBN/GO promoted the proliferation and alkaline phosphatase (ALP) activity of hDPSCs. In addition, qRT-PCR showed that MBN/GO regulated the mRNA levels of odontogenic markers (dentin sialophosphoprotein (DSPP), dentine matrix protein 1 (DMP-1), ALP, matrix extracellular phosphoglycoprotein (MEPE), bone morphogenetic protein 2 (BMP-2), and runt-related transcription factor 2 (RUNX-2)). The mRNA levels of DSPP and DMP-1, two odontogenesis-specific markers, were considerably upregulated in hDPSCs in response to growth on the MBN/GO composites. Western blot analysis revealed similar results. Alizarin red S staining was subsequently performed to further investigate MBN/GO-induced mineralization of hDPSCs. It was revealed that MBN/GO composites promote odontogenic differentiation via the Wnt/β-catenin signaling pathway. Collectively, the results of the present study suggest that MBN/GO composites may promote the differentiation of hDPSCs into odontoblast-like cells, and potentially induce dentin formation.

The purpose of this study was to assess the effects in the dentin bond strength of dental adhesives (DAs) and biological effects using zinc (Zn)-doped mesoporous bioactive glass nanoparticles (MBN-Zn). Synthesized MBN and MBN-Zn were characterized by scanning electron microscopy (SEM), X-ray diffraction and the Brunauer, Emmett and Teller (BET) method. The matrix metalloproteinases (MMP) inhibition effects of DA-MBN and DA-MBN-Zn were analyzed. The microtensile bond strength (MTBS) test was conducted before and after thermocycling to investigate the effects of MBN and MBN-Zn on the MTBS of DAs. The biological properties of DA-MBN and DA-MBN-Zn were analyzed with human dental pulp stem cells (hDPSCs). Compared with the DA, only the DA-1.0% MBN and DA-1.0% MBN-Zn exhibited a statistically significant decrease in MMP activity. The MTBS values after thermocycling were significantly increased in DA-1.0% MBN and DA-1.0% MBN-Zn compared with the DA (p < 0.05). It was confirmed via the MTT assay that there was no cytotoxicity for hDPSCs at 50% extract. In addition, significant increases in the alkaline phosphatase activity and Alizarin Red S staining were observed only in DA-1.0%MBN-Zn. These data suggest the 1.0% MBN and 1.0% MBN-Zn enhance the remineralization capability of DAs and stabilize the long-term MTBS of DAs by inhibiting MMPs.

Accumulating evidence suggests a link between periodontal disease and cardiovascular diseases. Vascular calcification is the pathological precipitation of phosphate and calcium in the vasculature and is closely associated with increased cardiovascular risk and mortality. In this study, we have demonstrated that the infection with Porphyromonas gingivalis (P. gingivalis), one of the major periodontal pathogens, increases inorganic phosphate-induced vascular calcification through the phenotype transition, apoptosis, and matrix vesicle release of vascular smooth muscle cells. Moreover, P. gingivalis infection accelerated the phosphate-induced calcium deposition in cultured rat aorta ex vivo. Taken together, our findings indicate that P. gingivalis contributes to the periodontal infection-related vascular diseases associated with vascular calcification.

Vascular calcification is the pathological deposition of calcium/phosphate in the vascular system and is closely associated with cardiovascular morbidity and mortality. Here, we investigated the role of gastrin-releasing peptide (GRP) in phosphate-induced vascular calcification and its potential regulatory mechanism. We found that the silencing of GRP gene and treatment with the GRP receptor antagonist, RC-3095, attenuated the inorganic phosphate-induced calcification of vascular smooth muscle cells (VSMCs). This attenuation was caused by inhibiting phenotype change, apoptosis and matrix vesicle release in VSMCs. Moreover, the treatment with RC-3095 effectively ameliorated phosphate-induced calcium deposition in rat aortas ex vivo and aortas of chronic kidney disease in mice in vivo. Therefore, the regulation of the GRP-GRP receptor axis may be a potential strategy for treatment of diseases associated with excessive vascular calcification.

Pentraxin-3 (PTX3) is recognized as a modulator of inflammation and a mediator of tissue repair. In this study, we characterized the role of PTX3 on some biological functions of human dental pulp stem cells (HDPSCs). The expression level of PTX3 significantly increased during osteogenic/odontogenic differentiation of HDPSCs, whereas the knockdown of PTX3 decreased this differentiation. Silencing of PTX3 in HDPSCs inhibited their migration and C-X-C chemokine receptor type 4 (CXCR4) expression. Our present study indicates that PTX3 is involved in osteogenic/odontogenic differentiation and migration of HDPSCs, and may contribute to the therapeutic potential of HDPSCs for regeneration and repair.

Hispidulin is a natural bioactive flavonoid that has been studied for its potential therapeutic properties, including its anti-inflammatory, antioxidant, and neuroprotective effects. The aim of this study was to explore whether hispidulin could inhibit the endothelial inflammation triggered by Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS). The adhesion of monocytes to the vascular endothelium was evaluated through in vitro and ex vivo monocyte adhesion assays. We analyzed the migration of monocytes across the endothelial layer using a transmigration assay. The results showed that treatment with hispidulin decreased the P. gingivalis LPS-induced adhesion of monocytes to endothelial cells and their migration by suppressing the P. gingivalis LPS-triggered expression of intercellular adhesion molecule-1 (ICAM-1) through downregulating nuclear factor-қB (NF-қB). In addition, hispidulin inhibited P. gingivalis LPS-induced mitogen-activated protein kinases (MAPKs) and AKT in endothelial cells. Altogether, the results indicate that hispidulin suppresses the vascular inflammation induced by P. gingivalis LPS. Mechanistically, it prevents the adhesion of monocytes to the vascular endothelium and migration and inhibits NF-қB, MAPKs, and AKT signaling in endothelial cells.