Gingipain and oncostatin M synergistically disrupt kidney tight junctions in periodontitis-associated acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is characterized by rapid renal decline. Periodontitis, a chronic oral inflammatory disease, is increasingly associated with renal dysfunction. Although periodontitis is recognized as a contributor to kidney damage, the mechanisms linking it to AKI remain unclear. METHODS: This study explored the effects of Porphyromonas gingivalis (P. gingivalis) W83-infected periodontitis on AKI in C57BL/6J mice, using ischemia-reperfusion injury 55 days post-infection. Gingipain inhibitors, KYT-1 and KYT-36, were applied. Detection of P. gingivalis was performed using quantitative real-time polymerase chain reaction (qRT-PCR) and PCR, while transcriptome sequencing, qRT-PCR, immunohistochemistry, and immunofluorescence staining assessed renal damage. In vitro, HK-2 cells were exposed to P. gingivalis at a multiplicity of infection of 10 for 48 h, with inhibition by gingipain or oncostatin M (OSM). Disruption of tight junctions (TJs) was quantified using qRT-PCR, transepithelial electrical resistance, and cell counting kit-8 assays. RESULTS: Periodontitis worsened AKI, linked to P. gingivalis infection and renal TJ disruption in the kidney. P. gingivalis infection activated OSM expression, which correlated positively with gingipain. Significantly, OSM and gingipain might collaboratively contribute to the damage of renal TJs, with the reduced expression of TJ proteins. Suppressing gingipain activity presented itself as a protective strategy against the destruction of TJs and the attendant worsening of AKI due to periodontitis. CONCLUSIONS: Our study enhances the understanding of the interplay between periodontitis and AKI, highlighting the harmful impact of P. gingivalis in AKI.

Effect of margin designs and loading conditions on the stress distribution of endocrowns: a finite element analysis.

BACKGROUND: Margin designs and loading conditions can impact the mechanical characteristics and survival of endocrowns. Analyzing the stress distribution of endocrowns with various margin designs and loading conditions can provide evidence for their clinical application. METHODS: Three finite element analysis models were established based on the margin designs: endocrown with a butt-joint type margin (E0), endocrown with a 90° shoulder (E90), and endocrown with a 135° shoulder (E135). The E0 group involved lowering the occlusal surface and preparing the pulp chamber. The E90 group created a 90° shoulder on the margin of model E0, measuring 1.5 mm high and 1 mm wide. The E135 group featured a 135° shoulder. The solids of the models were in fixed contact with each other, and the materials of tooth tissue and restoration were uniform, continuous, isotropic linear elasticity. Nine static loads were applied, with a total load of 225 N, and the maximum von Mises stresses and stress distribution were calculated for teeth and endocrowns with different margin designs. RESULTS: Compared the stresses of different models under the same loading condition. In endocrowns, when the loading points were concentrated on the buccal side, the maximum von Mises stresses were E0 = E90 = E135, and when there was a lingual loading, they were E0 < E90 = E135. In enamel, the maximum von Mises stresses under all loading conditions were E0 > E90 > E135. In dentin, the maximum von Mises stresses of the three models were basically similar except for load2, load5 and load9. Compare the stresses of the same model under different loading conditions. In endocrowns, stresses were higher when lingual loading was present. In enamel and dentin, stresses were higher when loaded obliquely or unevenly. The stresses in the endocrowns were concentrated in the loading area. In enamel, stress concentration occurred at the cementoenamel junction. In particular, E90 and E135 also experienced stress concentration at the shoulder. In dentin, the stresses were mainly concentrated in the upper section of the tooth root. CONCLUSION: Stress distribution is similar among the three margin designs of endocrowns, but the shoulder-type designs, especially the 135° shoulder, exhibit reduced stress concentration.

Cognitive decline in Sprague-Dawley rats induced by neuroplasticity changes after occlusal support loss.

BACKGROUND: Tooth loss is closely related to cognitive impairment, especially affecting cognitive functions involving hippocampus. The most well-known function of the hippocampus is learning and memory, and the mechanism behind is neuroplasticity, which strongly depends on the level of brain-derived neurotrophic factor (BDNF). While research has delved into the possible mechanisms behind the loss of teeth leading to cognitive dysfunction, there are few studies on the plasticity of sensory neural pathway after tooth loss, and the changes in related indicators of synaptic plasticity still need to be further explored. METHODS: In this study, the bilateral maxillary molars were extracted in Sprague-Dawley rats of two age ranges (young and middle age) to establish occlusal support loss model; then, the spatial cognition was tested by Morris Water Maze (MWM). Quantitative real-time PCR (qPCR) and Western Blotting (WB) were used to detect BDNF, AKT, and functional proteins (viz., PSD95 and NMDAR) of hippocampal synapses. Golgi staining was used to observe changes in ascending nerve pathway. IF was used to confirm the location of BDNF and AKT expressed in hippocampus. RESULTS: MWM showed that the spatial cognitive level of rats dropped after occlusal support loss. qPCR, WB, and IF suggested that the BDNF/AKT pathway was down-regulated in the hippocampus. Golgi staining showed the neurons of ascending sensory pathway decreased in numbers. CONCLUSION: Occlusal support loss caused plastic changes in ascending nerve pathway and induced cognitive impairment in rats by down-regulating BDNF and synaptic plasticity.

Photothermal-promoted multi-functional gallic acid grafted chitosan hydrogel containing tannic acid miniaturized particles for peri-implantitis.

Peri-implantitis, a leading cause of implant failure, currently lacks effective therapeutic strategies. Given that bacterial infection and reactive oxygen species overabundance serve as primary pathogenic and triggering factors, respectively, an adhesive hydrogel has been created for in-situ injection. The hydrogel is a gallic acid-grafted chitosan (CS-GA) hydrogel containing tannic acid miniaturized particles (TAMP). This provides antibacterial and antioxidant properties. Therefore, this study aims to evaluate the potential role of this hydrogel in preventing and treating peri-implantitis via several experiments. It undergoes rapid formation within a span of over 20 s via an oxidative crosslinking reaction catalyzed by horseradish peroxidase and hydrogen peroxide, demonstrating robust adhesion, superior cell compatibility, and a sealing effect. Furthermore, the incorporation of TAMP offer photothermal properties to the hydrogel, enabling it to enhance the viability, migration, and antioxidant activity of co-cultured human gingival fibroblasts when subjected 0.5 W/cm2 808 nm near-infrared (NIR) irradiation. At higher irradiation power, the hydrogel exhibits progressive improvements in its antibacterial efficacy against Porphyromonas gingivalis and Fusobacterium nucleatum. It attains rates of 83.11 ± 5.42 % and 83.48 ± 6.855 %, respectively, under 1 W/cm2 NIR irradiation. In summary, the NIR-controlled CS-GA/TAMP hydrogel, exhibiting antibacterial and antioxidant properties, represents a promising approach for the prophylaxis and management of peri-implantitis.

Effect of Porous Zirconia Coating on Human Gingival Fibroblasts and Its Mechanism.

Gingival fibroblasts play an important role in the constitution of soft tissue attachment. This study aims to investigate whether porous zirconia coating has a positive effect on promoting human gingival fibroblast attachment. The porous zirconia coating was loaded on zirconia surface by the dip coating method, surface morphology and composition were confirmed by scanning electron microscope and energy dispersive spectrometer; Tested the tensile bond strength by universal testing machine; Tested the surface roughness by roughness analyzer; Human gingival fibroblast proliferation, integrin ß1 and F-actin immunofluorescence staining explored the influence of porous zirconia on the adhesion and proliferation of human gingival fibroblast. Zirconia0.2 group showed spherical zirconia particles with diameters of 3-8 µm are distributed on the surface; The bonding strength of zirconia particle coating group reached 16.1±0.1 MPa, and the surface roughness was 0.715±0.091 µm; In comparison with control group (P < 0.01), the percentage of human gingival fibroblasts adhering to zirconia was markedly higher. In zirconia group, integrin-ß1 and F-actin fluoresced more obvious than in control group. Porous zirconia coating can form a porous structure on the surface and the porous structure can promote the attachment and proliferation of human gingival fibroblast, it will be more beneficial for soft tissue early sealing.

Tooth Loss Suppresses Hippocampal Neurogenesis and Leads to Cognitive Dysfunction in Juvenile Sprague-Dawley Rats.

Background: Both animal studies and prospective observational studies on patients with neurodegenerative disease have reported a positive link between oral diseases and cognitive function. However, the effect of early tooth loss on hippocampal morphology remains unknown. Methods: In this study, 6-week-old, male, juvenile Sprague-Dawley (SD) rats were randomized into the control (C) and tooth loss (TL) groups. In the TL group, all right maxillary molars of SD rats were extracted, while in the C group, no teeth were extracted. After 3 months, the learning and memory behavior were examined by Morris Water Maze (MWM), and the protein expression and mechanic signaling pathways were analyzed by real-time polymerase chain reaction, and cresyl violet staining. Results: Two days after the operation, the body weight of both groups recovered and gradually returned to the level before operation. Three months after tooth extraction, the completion time of the C group in the MWM was significantly shorter than the TL group. The mRNA expression of BDNF, TrkB, AKT1, and NR2B in the C group were significantly higher than in the TL group. The pyramidal neurons in the TL group was fewer than in the C group. Conclusion: Tooth loss in the juvenile SD rats will reduce the number of pyramidal neurons in the hippocampus, inhibit the expression of BDNF, TrkB, AKT1, and NR2B, and eventually lead to cognitive dysfunction.

Tooth Loss-Associated Mechanisms That Negatively Affect Cognitive Function: A Systematic Review of Animal Experiments Based on Occlusal Support Loss and Cognitive Impairment.

BACKGROUND: There is a dose-response relationship between tooth loss and cognitive impairment, while tooth loss can be an independent risk factor for Alzheimer's disease (AD) and vascular dementia (VaD). Tooth loss can also accelerate nerve damage and neurodegeneration. However, the associated mechanisms remain poorly understood. OBJECTIVE: To conduct a systematic review of animal experiments on cognitive decline caused by the loss of occlusal support performed over the past 10 years and summarize the possible underlying mechanisms. METHODS: "Tooth Loss," "Edentulous," "Tooth Extraction and Memory Loss," "Cognition Impairment," and "Dementia" were used as keywords to search PubMed, Embase, SCI, ScienceDirect, and OpenGrey. A total of 1,317 related articles from 2010 to 2021 were retrieved, 26 of which were included in the review after screening according to predetermined inclusion and exclusion criteria. Comprehensiveness was evaluated using ARRIVE guidelines and the risk of bias was assessed using SYCLE'S risk of bias tool. RESULTS: The putative mechanisms underlying the cognitive impairment resulting from the loss of occlusal support are as follows: (1) The mechanical pathway, whereby tooth loss leads to masticatory motor system functional disorders. Masticatory organ activity and cerebral blood flow decrease. With reduced afferent stimulation of peripheral receptors (such as in the periodontal membrane) the strength of the connections between neural pathways is decreased, and the corresponding brain regions degenerate; (2) the aggravation pathway, in which tooth loss aggravates existing neurodegenerative changes. Tooth loss can accelerates nerve damage through apoptosis and mitochondrial autophagy, increases amyloid deposition in the brain; and (3) the long-term inflammatory stress pathway, which involves metabolic disorders, microbial-gut-brain axis, the activation of microglia and astrocytes, and inflammatory cascade effect in central nervous system. CONCLUSION: The loss of occlusal support may lead to cognitive dysfunction through the reduction of chewing-related stimuli, aggravation of nerve damage, and long-term inflammatory stress.

Differential Expression and Distinct Roles of Proteinase-Activated Receptor 2 in Microglia and Neurons in Neonatal Mouse Brain After Hypoxia-Ischemic Injury.

Regulation of microglial activation and neuroinflammation are critical factors in the pathogenesis of ischemic brain injury. Interest in protease-activated receptor 2 (PAR2) as a pharmaceutical target for various diseases is creasing. However, it is unclear the expression and functions of PAR2 in hypoxia-ischemic (HI) brain injury. Mice with HI and cells with oxygen-glucose deprivation and reoxygenation (OGD/R) were studied. Immunoblot and qRT-PCR were used to study the differential gene expression in cultured microglia and neurons. Immunofluorescent staining was used to study the expression pattern of PAR2 in the HI brain and phagocytotic activity of microglia after OGD/R. In neonatal mice brain after HI, we found PAR2 expression was abundant in neurons, but barely in microglia from the contralateral side of cortex and hippocampus. Conversely, PAR2 expression was barely in neurons while significantly increased in activated microglia from the ipsilateral side of cortex and hippocampus. The activations of PAR2 were increased in both microglia and neuron in a cell model of OGD/R. PAR2 activation mediated the cross-talk between microglia and neurons including the following: microglial PAR2 mediated inflammatory responses that induced neuronal damage; neuronal PAR2 regulated chemokines that recruited activated microglia to damage area; microglia PAR2 controlled the phagocytosis of degenerating neurons. These data suggested differential expression and distinct roles of PAR2 in microglia and neurons after HI injury; thereby, interventions targeting PAR2 may provide insights into the inflammatory-related diseases.

Effect of titanium or zirconia implant abutments on epithelial attachments after ultrasonic cleaning.

Zirconia is widely employed as a material during dental implant work because of its superior esthetics. This study sought to evaluate the impact of titanium or zirconia implant abutments on epithelial attachments after ultrasonic cleaning. These implants were inserted into the extraction socket of rat maxillary first molars. Then, the length of the horseradish peroxidase (HRP) reaction was measured. In addition, titanium and zirconia disks were cleaned using an ultrasonic scaler, surface morphology changes were observed, and the number of epithelial cell attachments to the surface was measured. Ultimately, the surfaces of the titanium disks were easier to damage than those of the zirconia ones. There was no difference in the number of epithelial cell attachments between the two materials with the ultrasonic cleaning. The length of the HRP reaction was shorter on the zirconia implant abutment surface than on the titanium one after mechanical cleaning. In conclusion, zirconia is harder than titanium and a better choice for use in the epithelial tissue attachment. Zirconia is more suitable as a material for implant abutments than titanium.

Effects of Different Divalent Cation Hydrothermal Treatments of Titanium Implant Surfaces for Epithelial Tissue Sealing.

The improvement of peri-implant epithelium (PIE) adhesion to titanium (Ti) may promote Ti dental implant stability. This study aims to investigate whether there is a positive effect of Ti hydrothermally treated (HT) with calcium chloride (CaCl2), zinc chloride (ZnCl2), and strontium chloride (SrCl2) on promoting PIE sealing. We analyzed the response of a rat oral epithelial cell (OEC) culture and performed an in vivo study in which the maxillary right first molars of rats were extracted and replaced with calcium (Ca)-HT, zinc (Zn)-HT, strontium (Sr)-HT, or non-treated control (Cont) implants. The OEC adhesion on Ca-HT and Zn-HT Ti plates had a higher expression of adhesion proteins than cells on the Cont and Sr-HT Ti plates. Additionally, the implant PIE of the Ca-HT and Zn-HT groups revealed better expression of immunoreactive laminin-332 (Ln-322) at 2 weeks after implantation. The Ca-HT and Zn-HT groups also showed better attachment at the implant-PIE interface, which inhibited horseradish peroxidase penetration. These results demonstrated that the divalent cations of Ca (Ca2+) and Zn (Zn2+)-HT improve the integration of epithelium around the implant, which may facilitate the creation of a soft barrier around the implant to protect it from foreign body penetration.

The impact of surface alteration on epithelial tissue attachment after the mechanical cleaning of titanium or zirconia surface.

OBJECTIVE: Mechanical plaque removal may alter the surface morphology of the gingival penetration part of the implant. We applied an air-powered abrasive system (AP), titanium curette (TC), stainless curette (SC), ultrasound scaler (US), and titanium brush (TB) which are commonly used to remove plaque, to titanium or zirconia and the changes in surface morphology and the epithelial attach against substrata. MATERIALS AND METHODS: (a) The morphological changes of titanium and zirconia after mechanical cleaning were assessed by scanning electron microscopy and a roughness analyser. (b) Oral epithelial cells of rats were inoculated on the surface of the materials after mechanical cleaning, and the adherence of epithelial cells was observed. (c) The maxillary first molars were extracted from the rats and replaced by experimental titanium or zirconia implants. The length of the immunoreactive laminin-332 band was observed at the implant-peri-implant epithelium interface. RESULTS: (a) The surface roughness increased in experimental groups except the AP group. (b) Among the experimental groups, the AP group showed the highest number of attached cells. (c) The length of the immunoreactive laminin-332 band was longer in the control group than those in all five experimental groups. Among the experimental groups, the AP group showed the longest band. CONCLUSION: All mechanical cleaning methods increased the surface roughness of the materials except AP. AP did not cause distinct implant surface alterations. Surface alteration caused by mechanical cleaning may evoke inferior for epithelial attachment and reduce resistance against foreign infiltration.

Effect of a Single Injection of Benidipine-Impregnated Biodegradable Microcarriers on Bone and Gingival Healing at the Tooth Extraction Socket.

Objective: A dihydropyridine-type calcium channel blocker, benidipine (BD), is extensively used in hypertension therapy. In vitro study reported BD promoting bone metabolism. We evaluated the effect of sustained release of BD-loaded poly(lactic-co-glycolic acid) (PLGA) microcarriers on the promotion of bone and gingival healing at an extraction socket in vivo. In addition, the effect of BD on osteoblasts, osteocytes, fibroblasts, and epithelial cells was evaluated in vitro. Approach: The maxillary first molar of rats was extracted. Next, PLGA microcarriers containing BD were directly injected into the gingivobuccal fold as a single dose. After injection, bone and soft-tissue healing was histologically evaluated. Effect of BD on proliferation, migration, and gene expression of gingival and bone cell was also examined in vitro. Results: After tooth extraction, BD significantly augmented bone volume and density, and also epithelial wound healing. During in vitro studies, BD promoted significant proliferation and migration of fibroblasts and epithelial cells. Real-time RT-PCR revealed that BD upregulated messenger RNA expression of Ahsg (alpha 2-HS glycoprotein) and Csf2 (colony-stimulating factor 2) in osteoblasts. Innovation: The prevention of bone and soft-tissue reduction associated with tooth extraction has been eagerly anticipated in the field of dentistry. This study first reported the effect of BD on extraction socket healing. Conclusion: A single dose of topically administered BD-loaded PLGA microcarriers promoted bone and soft-tissue healing at the extraction site of tooth.

Injectable Porous Bioresorbable Composite Containing Fluvastatin for Bone Augmentation.

The purpose of this study was to evaluate the effects of an injectable composite made up of calcium sulfate (CAS), fluvastatin (FS), and atelocollagen on bone augmentation in rats. Porous structures and compressive strength of composites were evaluated. The cumulative release kinetics of FS were determined in vitro by a spectrophotometer. To observe bone regeneration in vivo, five different materials (normal saline; atelocollagen gel only; composite of CAS and atelocollagen; composite containing 0.5% FS; and composite containing 1.0% FS) were injected in extraction sockets and in the crania of rats. Microcomputed tomography and histological evaluation were performed after 2, 4, and 8 weeks of healing time. The composites had high porosity (greater than 55%). FS kept a slow and stable release for >30 days. In vivo results demonstrated that more new bone was formed in the FS groups compared with the other groups, and both bone mass and bone density had prominent increase in maxillae and crania. Resorption of the composite was also observed for cranial tissues. In conclusion, this composite can be applied percutaneously, without any incision. It has excellent properties with replaceability into bone and anabolic effects for bone formation, as well as a drug delivery system for bone formation.