Diabetes mellitus promotes susceptibility to periodontitis-novel insight into the molecular mechanisms.

Diabetes mellitus is a main risk factor for periodontitis, but until now, the underlying molecular mechanisms remain unclear. Diabetes can increase the pathogenicity of the periodontal microbiota and the inflammatory/host immune response of the periodontium. Hyperglycemia induces reactive oxygen species (ROS) production and enhances oxidative stress (OS), exacerbating periodontal tissue destruction. Furthermore, the alveolar bone resorption damage and the epigenetic changes in periodontal tissue induced by diabetes may also contribute to periodontitis. We will review the latest clinical data on the evidence of diabetes promoting the susceptibility of periodontitis from epidemiological, molecular mechanistic, and potential therapeutic targets and discuss the possible molecular mechanistic targets, focusing in particular on novel data on inflammatory/host immune response and OS. Understanding the intertwined pathogenesis of diabetes mellitus and periodontitis can explain the cross-interference between endocrine metabolic and inflammatory diseases better, provide a theoretical basis for new systemic holistic treatment, and promote interprofessional collaboration between endocrine physicians and dentists.

Experimental study of dexamethasone-loaded hollow hydroxyapatite microspheres applied to direct pulp capping of rat molars.

Background: Dexamethasone (DEX) exerts anti-inflammatory and osteogenic effects. Hydroxyapatite is commonly used in bone repair due to its osteoconductivity, osseointegration, and osteogenesis induction. Hollow hydroxyapatite (HHAM) is often used as a drug carrier. Objective: This study aimed to investigate the histological responses of exposed dental pulp when dexamethasone-loaded nanohydroxyapatite microspheres (DHHAM) were used as a direct capping agent. Methods: Cavities were created in the left maxillary first molar of Wistar rats and filled with Dycal, HHAM, and DHHAM. No drug was administered to the control group. The rats were sacrificed at 1, 2, and 4 weeks after the procedure. The molars were extracted for fixation, demineralization, dehydration, embedding, and sectioning. H&E staining was performed to detect the formation of reparative dentin. H&E and CD45 immunohistochemical staining were performed to detect pulp inflammation. Immunohistochemical staining was performed to assess the expressions of dentin matrix protein 1 (DMP-1), interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1ß. Results: The results of H&E and CD45 immunohistochemical staining showed that the degree of inflammation in the DHHAM group was less than that in the Control and HHAM groups at 1, 2, and 4 weeks after capping of the rat molar teeth (p<0.01). The H&E staining showed that the percentage of reparative dentin formed in the DHHAM group was higher than that in the Control, HHAM (p<0.001), and Dycal groups (p<0.01) at 1 and 2 weeks, and was significantly higher than that in the Control group (p<0.001) and the HHAM group (p<0.01) at 4 weeks. The immunohistochemical staining showed a lower range and intensity of expression of IL-1ß, IL-6, and TNF-α and high expression levels of DMP-1 in the DHHAM group at 1, 2, and 4 weeks after pulp capping relative to the Control group. Conclusions: DHHAM significantly inhibited the progression of inflammation and promoted reparative dentin formation.

Effect of oligonucleotide MT01 delivered by N-isopropylacrylamide modified polyethyleneimine for bone regeneration.

Objective: This study aimed to investigate the regulatory effect of N-isopropylacrylamide-modified polyethyleneimine (PEN)-delivered oligodeoxynucleotide (ODN) MT01 on bone regeneration in vitro and in vivo. Methods: A polyethylenimine (PEI) derivative, PEN, was constructed through Michael addition and employed as a carrier for ODN MT01 transfection. PEN/MT01 nanocomposites were characterized using agarose gel retardation assay, size distribution, zeta potential and transmission electron microscopy. The Cell Counting Kit-8 (CCK-8) assay was used to detect the effect of PEN on cell viability. Alkaline phosphatase (ALP) staining was used to detect the osteogenic differentiation ability of PEN/MT01 nanocomposite. Real-time quantitative PCR (q RT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the regulatory effects of PEN/MT01 nanocomposite on osteogenic differentiation gene expression. Rat model was observed using the skull defect method and verified using micro-computed tomography (CT), serum biochemical indices, hematoxylin and eosin (H&E) staining and Immunohistochemistry (IHC). Results: PEN had good biological properties and could deliver MT01 well to achieve efficient transmission of MT01. PEN/MT01 nanocomposites were effectively transfected into MC3T3-E1 cells at a ratio of 6.0. CCK-8 assay displayed that PEN had no cytotoxicity to MC3T3-E1 cells. Additionally, PEN/MT01 nanocomposites could promote the expression of osteogenic genes. In vivo results revealed that PEN/MT01 nanocomposites could promote bone regeneration more effectively than the other groups. Conclusion: PEN has good biocompatibility and low toxicity, which is a good carrier for ODN MT01. PEN-delivered MT01 can be potentially employed as a useful approach to achieving bone regeneration.

Metformin carbon nanodots promote odontoblastic differentiation of dental pulp stem cells by pathway of autophagy.

Human dental pulp stem cells (hDPSCs) have been a focus of pulp regeneration research because of their excellent odontogenic potential and availability. Applying the odontoblastic differentiation of hDPSCs to tooth regeneration has been challenging. Metformin-based carbon nanodots (MCDs) were synthesized and characterized to investigate their effects in vitro on odontoblastic hDPSC differentiation and the underlying mechanism. MCDs were synthesized by a hydrothermal treatment method and characterized using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The biocompatibility and fluorescence properties of the MCDs in Dulbecco's modified Eagle's medium high-glucose culture medium and the in vitro odontogenic potential and related mechanism of the bioactive nanomaterial was explored. TEM images showed that MCDs were spherical in shape with a size of approximately 5.9 nm. MCDs showed biological safety in cell viability, apoptosis, and fluorescence labelling ability at a concentration up to 200 µg/ml in vitro. The presence of MCDs facilitated high-efficiency odontogenic differentiation of hDPSCs by promoting odontogenic gene and protein expression. Moreover, MCDs promoted odontoblastic hDPSC differentiation via autophagy. MCDs are capable of activating autophagy and enhancing the odontogenic differentiation of hDPSCs by upregulating odontoblast gene marker (DMP1, DSPP, RUNX2, and SP7) and protein (DSPP and DMP1) expression.