Phytic acid improves osteogenesis and inhibits the senescence of human bone marrow mesenchymal stem cells under high-glucose conditions via the ERK pathway.

Hyperglycaemia causes impairment of osteogenic differentiation and accelerates stem cell senescence, resulting in weakened osteogenesis and disordered bone metabolism. Phytic acid (PA) is an antioxidant that is reportedly beneficial to bone homeostasis. The present study aims to clarify how PA affects the osteogenic capacity and cellular senescence of bone marrow mesenchymal stem cells (BMSCs) exposed to high-glucose environments, as well as the potential molecular mechanisms. Our results indicate that osteogenic differentiation in BMSCs cultivated in high-glucose conditions is enhanced by PA, as evidenced by increased alkaline phosphatase activity and staining, Alizarin Red S staining, osteogenic marker in in vitro studies, and increased osteogenesis in animal experiments. PA also prevented high-glucose-induced senescence of BMSCs, as evidenced by the repression of reactive oxygen species production, senescence-associated ß-galactosidase staining, and P21 and P53 expression. Furthermore, it was found that PA rescued the high-glucose-inhibited expression of phosphorylated extracellular regulated protein kinases (p-ERK). The inhibition of ERK pathway by the specific inhibitor PD98059 blocked the PA-enhanced osteogenesis of BMSCs and promoted cell senescence. Our results revealed that PA enhances osteogenic differentiation and inhibits BMSC senescence in a high-glucose environment. In addition, the activation of the ERK pathway seems to mediate the beneficial effects of PA. The findings provide novel insights that could facilitate bone regeneration in patients with diabetes.

Bioinspired Synthesis of Ag Nanoparticles onto Polytetrafluoroethylene with Enhanced Antibacterial Activity for Dental Implant Application.

BACKGROUND: Endosseous implants are widely used as a treatment for tooth loss, but gaps in the implant-abutment interface, and the cavity inside the implant, can cause inflammation of the tissue surrounding the implant. Currently available filling materials, however, cannot solve these problems. Therefore, the development of new antibacterial materials is key. In this study, we synthesized Ag nanoparticle-coated polytetrafluoroethylene (PTFE), analyzed the effect of Ag ion concentration, and estimated the antibacterial effects against oral pathogens in vitro. Method: The Ag nanoparticles (AgNPs)-modified PTFE was achieved using self-polymerized dopamine in an alkaline solution (2 mg/mL) and reduction reaction of Ag ions (0.01 mol/L and 0.05 mol/L). The surface features, chemical components, and wettability were characterized by scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS) and contact angle measurement. The antibacterial effect against Streptococcus mutans and Porphyromonas gingivalis was evaluated by counting colony-forming units on agar media and the visualization of bacteria present on the specimens by SEM and confocal laser scanning microscope (CLSM). RESULTS: The surface characterization results indicated that a polydopamine film was successfully formed on the PTFE membrane, and spherical AgNPs were successfully reduced. With increasing concentration of the Ag precursor, the contents of the AgNPs increased (p < 0.05). The antibacterial ratio of AgNP-coated PTFE against Streptococcus mutans and Porphyromonas gingivalis reached 94.2% and 80.6%, respectively. The results of antibacterial testing analyzed via SEM and CLSM also demonstrated the robust antibacterial ability of AgNPs-modified PTFE (p < 0.05). CONCLUSIONS: AgNPs-modified PTFE has great potential to function as an implant filling material with enhanced antibacterial properties, and has the potential to be a novel antimicrobial material for the prevention of peri-implantitis in the clinic.

Rescuing effects of periostin in advanced glycation end-products (AGEs) caused osteogenic and oxidative damage through AGE receptor mediation and DNA methylation of the CALCA promoter.

An in vitro model was established to simulate a diabetes-type environment by treating human periodontal stem cells with advanced glycation end-products (AGEs). Periostin (POSTN) plays a crucial role in maintaining the integrity of periodontal tissues. However, the role of POSTN in human periodontal stem cells stimulated by AGEs remains unknown. Diabetes mellitus is considered a metabolic disease, and DNA methylation of CpG islands is a biomarker of metabolic syndromes. Diabetes has been found to be closely related to the DNA methylation of certain genes. Here, we investigated the protective mechanism and effect of POSTN on osteogenesis and oxidative stress in the AGE environment, and further explored the CpG island methylation of specific genes potentially mediated by POSTN. The optimal concentration of AGEs was screened using CCK8. AGEs were found to contribute to oxidative stress. Conversely, reactive oxygen species production and malondialdehyde and superoxide activity indicated that the AGE + POSTN group decreased oxidative injury. According to an alkaline phosphatase assay, Alizarin Red S staining, and the expression of key genes and proteins involved in osteogenesis, POSTN mitigated the inhibitory effects of AGE on cell proliferation and osteogenic differentiation potential during osteogenic differentiation. In contrast, the growth and osteogenesis of human periodontal stem cells were notably suppressed by POSTN knockdown. Bisulfite sequencing PCR was used to evaluate the DNA methylation status. Moreover, AGE elevated the expression of DNA methyltransferas 1 (DNMT1) and inhibited the activation of CALAL promoter methylation, which was rescued by the addition of POSTN and 5-Azacytidine (5-AZA). In conclusion, POSTN attenuated the AGE-induced inhibition of osteogenesis in periodontal ligament stem cells by reducing AGE receptor levels and DNA methylation of the calcitonin-related polypeptide α (CALCA) promoter. Thus, POSTN is a promising candidate for dental bone regeneration, representing a novel therapeutic agent for diabetic patients. The mechanism underlying these processes may provide new insights into novel therapeutic targets for improving abnormal bone metabolism in patients with diabetes.

Clinical assessment of pterygoid and anterior implants in the atrophic edentulous maxilla: a retrospective study.

OBJECTIVES: This study aims to evaluate the short-term clinical outcomes and patient satisfaction of anterior and pterygoid implants in the rehabilitation of edentulous maxilla with posterior atrophy. METHODS: Given a minimum follow-up of 1 year, 25 patients with fixed maxillary rehabilitation over anterior and pterygoid implants were enrolled in this retrospective study. The implant survival rates, peri-implant soft tissue status (including probing depth, modified sulcus bleeding index, and plaque index), marginal bone loss, and patient satisfaction were measured. RESULTS: The survival rates for anterior and pterygoid implants at 1-year follow-up were 96.5% and 97.8%, respectively (P>0.05). No statistically significant difference in probing depth, modified sulcus bleeding index, and plaque index was observed between the two types of implants (P>0.05). The marginal bone losses of anterior implants were 0.62 mm± 0.44 mm (mesial) and 0.61 mm± 0.40 mm (distal), and those of pterygoid implants were 0.64 mm± 0.46 mm (mesial) and 0.68 mm± 0.41 mm (distal) mm. These results showed no statistical difference in mesial and distal sites (P>0.05). Patients indicated a high degree of satisfaction with the full-arch prostheses supported by anterior and pterygoid implants. CONCLUSIONS: For the edentulous maxilla with posterior atrophy, full-arch fixed prostheses supported by anterior and pterygoid implants has an acceptable short-term clinical outcome and excellent patient satisfaction. It may be considered as a predictable and feasible method for maxillary rehabilitation.

[Effect of individualized healing abutment on patients with posterior implant prosthesis and improvement of food impaction symptoms].

PURPOSE: To observe the effect of individualized healing abutment on patients with posterior dental implant prosthesis and its influence on implant stability and food impaction. METHODS: Eighty patients who received posterior dental implants in Jiangsu Stomatological Hospital from June 2013 to June 2018 were selected as the study subjects. According to the different healing abutment, they were divided into traditional operation group (40 cases) and experimental group (40 cases). Patients in the experimental group used personalized healing abutment on the basis of traditional dental implants. Differences in dental implant stability, food impaction score, masticatory efficiency and incidence of complications between the two groups after implant restoration were compared. SPSS 13.0 software package was used to analyze the data. RESULTS: At 1, 3 and 6 months after operation, the stability of implants in the experimental group was significantly higher than that in the control group (P<0.01); One, 3 and 6 months after operation, the food impaction score in the experimental group was significantly lower than that in the traditional operation group(P<0.01); There was no significant difference in masticatory ability between the two groups before operation; After treatment, the occlusive force and masticatory efficiency in the experimental group were significantly higher than those in the traditional operation group (P<0.05). The incidence of complications such as tooth loosening and periodontitis in the experimental group was significantly lower than in the traditional operation group (P<0.05). CONCLUSIONS: Individualized healing abutment has a good therapeutic effect on patients with posterior implant prosthesis, and can significantly improve the incidence of food impaction and complications with a good application value.

[Effect of LncTUG1 on NK cell killing sensitivity in oral squamous cell carcinoma cells by targeting miR-212-3p].

PURPOSE: To investigate the effect of LncTUG1 on NK cell killing sensitivity in oral squamous cell carcinoma cells. METHODS: Oral squamous cell carcinoma cells were used as experimental objects in vitro. TUG1 siRNA was transfected,the expression of TUG1, cell proliferation, cell apoptosis and NK cell killing rate were detected by qRT-PCR, MTT, flow cytometry and LDH. Bioinformatics software was used to predict that TUG1 and miR-212-3p will target and complement each other, so luciferase reporter vector was constructed and the targeting relationship was identified. TUG1 siRNA and miR-212-3p inhibitor were co-transfected into oral squamous cell carcinoma cells, the effects of miR-212-3p inhibitor on TUG1 siRNA on proliferation, apoptosis and NK cell killing sensitivity of oral squamous cell carcinoma cells were evaluated. The data were analyzed with SPSS 21.0 software package. RESULTS: TUG1 siRNA could significantly reduce the expression of TUG1 in oral squamous cell carcinoma cells (P=0.000), decrease cell proliferation (P=0.001), promote cell apoptosis (P=0.000), increase the killing rate of NK cells (P<0.01). TUG1 siRNA targeted to increase the expression of miR-212-3p. miR-212-3p inhibitor could reverse the effects of TUG1 siRNA on proliferation, apoptosis and NK cell killing rate of oral squamous cell carcinoma cells. CONCLUSIONS: Down-regulation of TUG1 targeting and negative regulation of miR-212-3p inhibits proliferation, induces apoptosis and improves NK cell killing sensitivity of oral squamous cell carcinoma cells.

Redox/pH dual-controlled release of chlorhexidine and silver ions from biodegradable mesoporous silica nanoparticles against oral biofilms.

BACKGROUND: Oral plaque biofilms pose a threat to periodontal health and are challenging to eradicate. There is a growing belief that a combination of silver nanoparticles and chlorhexidine (CHX) is a promising strategy against oral biofilms. PURPOSE: To overcome the side effects of this strategy and to exert maximum efficiency, we fabricated biodegradable disulfide-bridged mesoporous silica nanoparticles (MSNs) to co-deliver silver nanoparticles and CHX for biofilm inhibition. MATERIALS AND METHODS: CHX-loaded, silver-decorated mesoporous silica nanoparticles (Ag-MSNs@CHX) were fabricated after CHX loading, and the pH- and glutathione-responsive release profiles of CHX and silver ions along with their mechanism of degradation were systematically investigated. Then, the efficacy of Ag-MSNs@CHX against Streptococcus mutans and its biofilm was comprehensively assessed by determining the minimum inhibitory concentration, minimum bactericidal concentration, minimal biofilm inhibitory concentration, and the inhibitory effect on S. mutans biofilm formation. In addition, the biosafety of nanocarriers was evaluated by oral epithelial cells and a mouse model. RESULTS: The obtained Ag-MSNs@CHX possessed redox/pH-responsive release properties of CHX and silver ions, which may be attributed to the redox-triggered matrix degradation mechanism of exposure to biofilm-mimetic microenvironments. Ag-MSNs@CHX displayed dose-dependent antibacterial activity against planktonic and clone formation of S. mutans. Importantly, Ag-MSNs@CHX had an increased and long-term ability to restrict the growth of S. mutans biofilms compared to free CHX. Moreover, Ag-MSNs@CHX showed less cytotoxicity to oral epithelial cells, whereas orally administered Ag-MSNs exhibited no obvious toxic effects in mice. CONCLUSION: Our findings constitute a highly effective and safe strategy against biofilms that has a good potential as an oral biofilm therapy.

Antibacterial and biodegradable tissue nano-adhesives for rapid wound closure.

BACKGROUND: Although various organic tissue adhesives designed to facilitate would healing are gaining popularity in diverse clinical applications, they present significant inherent limitations, such as rejection, infections, toxicity and/or excessive swelling. It is highly desirable to develop efficient, biocompatible and anti-bacterial tissue adhesives for skin wound healing. PURPOSE: Inspired by the fact that inorganic nanoparticles can directly glue tissues through the "nanobridging effect", herein disulfide bond-bridged nanosilver-decorated mesoporous silica nanoparticles (Ag-MSNs) was constructed as an effective and safe tissue adhesive with antibacterial and degradable properties for wound closure and healing. MATERIALS AND METHODS: Ag-MSNs was fabricated by controlled reduce of ultrasmall nanosilvers onto the both surface and large pore of biodegradable MSNs. The obtained MSNs were characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, and measurement of size distribution, zeta potential, and mesopore properties. Furthermore, adhesion strength test, anti-bacterial assessment, mouse skin wound model, and MTT assays were used to investigate the tissue adhesive property, antibacterial effect, biodegradability and biocompatibility of the Ag-MSNs. RESULTS: Ag-MSNs exhibited not only strong adhesive properties but also excellent antibacterial activities than that of MSNs. Importantly, this antibacterial nano-adhesive achieved rapid and efficient closure and healing of wounds in comparison to sutures or MSNs in a mouse skin wound model. Furthermore, Ag-MSNs with fast degradable behavior caused little cellular toxicity and even less systemic toxicity during wound healing. CONCLUSION: Our findings suggest that biodegradable Ag-MSNs can be employed as the next generation of nano-adhesives for rapid wound closure and aesthetic wound healing.

Effect of titanium ions on the Hippo/YAP signaling pathway in regulating biological behaviors of MC3T3-E1 osteoblasts.

Titanium (Ti) and its corresponding alloys have been widely applied in dental and orthopedic implants. Owing to abrasion and corrosion of implants in the unfavorable electrolytic aqueous environment of the host body, Ti ions could be released from implants and accumulated in local tissues. Recent studies have found that excessive Ti ions were toxic to osteoblasts in adjacent bone tissues and subsequently influenced long-term effects on implant prostheses. However, the potential molecular mechanisms underlying the damage to osteoblasts induced by Ti ions remained unclear. Hippo signaling has been confirmed to be involved in organ size and tissue regeneration in many organs, while its roles in osteoblasts differentiation and bone repair remained elusive. Therefore, we hypothesize that YAP, a regulator of Hippo pathway, inhibited osteoblast growth, skeletal development and bone repair, as well as excessive Ti ions promoted the progression of YAP activation. This study aimed to explore the role of Hippo/YAP signaling pathway in the biotoxicity effect of Ti ions on osteoblast behaviors. Here, we confirmed that 10 ppm Ti ions, a minimum concentration gradient previously reported that was capable of suppressing osteoblasts growth, induced nuclear expression of YAP in osteoblasts in our study. Furthermore, 10 ppm Ti ion-induced YAP activation was found to downregulate osteogenic differentiation of MC3T3-E1 cells. Most importantly, the hypothesis we proposed that knockdown of YAP did reverse the inhibitory effect of 10 ppm Ti ions on osteogenesis has been verified. Taken together, our work provides insights into the mechanism of which YAP is involved in regulating osteoblast behaviors under the effect of Ti ions, which may help to develop therapeutic applications for Ti implant failures and peri-implantitis.

[A clinical analysis of screw-retained implant-supported casted integrated abutment crowns in the molar region with limited interocclusal space].

PURPOSE: To observe the clinical effects of screw-retained implant-supported casted abutment integrated crowns (IACs) in the molar region with limited interocclusal space. METHODS: This study involved 507 implants in 376 patients with limited interocclusal space in the molar region. All implants were inserted to the jaw by standard one-stage protocol. Screw-retained IACs were used as the final prosthesis. With 6 to 24 months follow-up, the clinical effects of screw-retained IACs were recorded and analyzed using SPSS 17.0 software package. RESULTS: During 6 to 24 months of follow-up, the implant survival rate was 99.61%. 37 patients had ceramic fracture which mainly happened in the group with 3-4 mm interocclusal space. In each group, porcelain fused to metal (PFM) prosthesis had ceramic fracture more easily than PFM prosthesis without porcelain on occlusal surface(P<0.05). As the interocclusal space became smaller, the probability of collapsing porcelain increased(P<0.05).13 patients had screw loosening. 13 patients suffered from gingival swelling and bleeding, they were given periodontal treatment and oral hygiene instruction. Patients were satisfied with the restoration results. CONCLUSIONS: Screw-retained IACs can be used to repair missing teeth in the molar region with limited interocclusal space.