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Background: Increasing evidence has shown that environmental factors play a crucial role in the pathogenesis of periodontitis. Humans are simultaneously exposed to a variety of environmental brominated flame retardants (BFRs). However, the relationship between BFRs in periodontitis remains unclear. This study aimed to investigate the overall association between BFRs and periodontitis in a nationally representative US population and to further identify important chemicals., Methods: Data from 3322 NHANES participants from 2009 to 2016 were used. Serum BFRs were registered, including PBDE-28, PBDE-47, PBDE-85, PBDE-99, PBDE100, PBDE-153, PBDE-154, PBDE-183, PBDE-209 and PBB-153. Survey weighted generalized logistic regression models, restricted cubic splines (RCS) were conducted to assess single BFRs exposure with periodontitis. Meanwhile, weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were used to evaluate the overall association of BFRs mixtures with periodontitis and to identify significant chemicals., Results: A total of 3322 participants were included in the study, of whom 1795 had periodontitis. After adjusting for potential confounders, multiple logistic regression analysis revealed significant positive associations between serum levels of PBDE-28, PBDE-47, PBDE-85, PBDE-99, PBDE-100, PBDE-154, PBDE-183, and PBB-153 and the risk of periodontitis (all P < 0.05). A dose-response relationship was observed for many of these BFRs, with higher quantiles associated with an increased risk of periodontitis. WQS regression identified PBDE-183 (38.60%), PBDE-153 (21.20%), PBDE-209 (14.40%), and PBDE-99 (11.90%) as the BFRs with the largest weights contributing to the overall mixture effect on periodontitis risk. BKMR analysis further supported the positive association between serum BFRs and periodontitis, with most individual BFRs showing a positive trend, except for PBDE-153. Restricted cubic spline analysis revealed a generally increasing probability of periodontitis with increasing concentrations of BFRs, albeit with some nonlinear patterns for certain compounds., Conclusion: In conclusion, this study provides compelling evidence of a significant association between exposure to brominated flame retardants (BFRs) and an increased risk of periodontitis in a nationally representative sample of U.S. adults. Elevated serum levels of several BFRs, including PBDE-28, PBDE-47, PBDE-85, PBDE-99, PBDE-100, PBDE-154, PBDE-183, and PBB-153, were found to be positively associated with periodontitis, exhibiting a dose-response relationship., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Immune checkpoint inhibitors (ICIs) cause immune-related adverse events (irAEs) across various organ systems including oral health complications such as dry mouth and stomatitis. In this study, we aimed to determine the risk of periodontitis among patients on immune checkpoint inhibitors (ICIs) and to test the associations between ICI-associated periodontitis and other immune-related adverse events (irAEs). We performed a retrospective cohort study involving adult cancer patients between January 2010 and November 2021. Patients on an ICI were propensity score-matched to patients not on an ICI. The primary outcome was the occurrence of periodontitis. ICIs included programmed cell death 1 (PD-1) inhibitors programmed cell death ligand 1 (PD-L1) inhibitors, and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors. The risk of periodontitis following ICI use was derived through a Cox proportional hazard model and Kaplan-Meier survival analysis. Overall, 868 patients on an ICI were matched to patients not on an ICI. Among the ICI cohort, 41 (4.7 %) patients developed periodontitis. The incidence rate of periodontitis was significantly higher in patients on an ICI than in patients not on an ICI (55.3 vs 25.8 per 100 patient-years, incidence rate ratio = 2.14, 95 % CI = 1.38-3.33). Both the use of PD-L1 inhibitors (multivariate HR = 2.5, 95%CI = 1.3-4.7) and PD-1 inhibitors (multivariate HR = 2.0, 95%CI = 1.2-3.2) were associated with the risk of periodontitis. The presence of immune-related periodontitis was associated with better overall survival (not reached vs 17 months, log-rank p-value<0.001), progression-free survival (14.9 vs 5.6 months, log-rank p-value = 0.01), and other concomitant immune-related cutaneous adverse events. In conclusion, ICI was associated with an increased risk of periodontitis. Immune-related periodontitis as an irAE was associated with better cancer survival and concomitant cutaneous irAEs., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Sullivan reported a consulting/advisory role with Marengo, Merck, Novartis, Pfizer, and Replimune. Dr. Sullivan is supported by funding by Merck., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aimed to determine if air pollution affected the risk of periodontitis outpatient visits. We collected the records of 56,456 periodontitis outpatient visits in Hefei, China, from January 1, 2014 to December 31, 2021. The relationship between air pollution and periodontitis outpatient visits was evaluated using distributed lag nonlinear and generalized linear models. Additional analyses were performed, stratifying the data by age, season, and sex. Subgroup analyses showed a significantly higher risk of periodontitis outpatient visits due to NO 2 exposure during the warm season compared with the cold season. Moreover, O 3 exposure was associated with a lower risk of periodontitis outpatient visits in the cold season. The findings suggest that NO 2 exposure is associated with an increased risk of periodontitis outpatient visits, whereas O 3 exposure is associated with a decreased risk of periodontitis outpatient visits. Season is found to be an effect modifier in these associations.

Background: Phthalates are widely used plasticizers, which were identified as risk factors in the development of many human diseases. However, the effects of phthalates in the periodontitis are unknown. We aimed to investigated the relationship of periodontitis and phthalate exposure as well as the underlying mechanisms., Materials and Methods: Univariate and multivariate logistic regressions were employed to evaluate the association between phthalate metabolites and periodontitis. The generalized additive model and piecewise logistic regression were conducted to investigate the dose-response relationship. Cell and animal models were used to explore the role and mechanism of DEHP in the development of periodontitis. Transcriptome sequencing, bioinformatics analysis, western blot, immunofluorescence and mice model of periodontitis were also employed., Results: MEHP (OR 1.14, 95% CI 1.05-1.24), MCPP (OR 1.08, 95% CI 1.00-1.17), MEHHP (OR 1.18, 95% CI 1.08-1.29), MEOHP (OR 1.18, 95% CI 1.07-1.29), MiBP (OR 1.15, 95% CI 1.04-1.28), and MECPP (OR 1.20, 95% CI 1.09-1.32) were independent risk factors. And MEHHP, the metabolite of DEHP, showed the relative most important effects on periodontitis with the highest weight (0.34) among all risk factors assessed. And the increase of inflammation and the activation of NFκB pathway in the periodontitis model mice and cells were observed., Conclusion: Exposure to multiple phthalates was positively associated with periodontitis in US adults between 30 and 80 years old. And DEHP aggravated inflammation in periodontitis by activating NFκB pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Yunvjian decoction (YNJ) is a traditional Chinese herbal prescription that has been used in the clinical treatment of periodontitis. However, the underlying molecular mechanism of YNJ in the periodontitis treatment is not well understood., Aim of the Study: The purpose of this study was to evaluate the therapeutic effects of YNJ against periodontitis and its underlying molecular mechanisms., Materials and Methods: Orthodontic ligation and lipopolysaccharide (LPS)-induced periodontitis rat model was established. YNJ groups were gavaged with YNJ decoction (5 g/kg/d or 10 g/kg/d) for four months. The rats in positive control group were gavaged with metronidazole (MDZ, 100 mg/kg/d) for four months. The maxilla was scanned by micro-computed tomography. The chemical compositions of YNJ were identified using ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry. The molecular mechanism of YNJ were predicted using network pharmacological analysis and validated using immune-staining and Western blot., Results: YNJ treatment decreased the distance between cementoenamel junction and alveolar bone crest on the sagittal slide of the periodontitis rats. Western blot showed YNJ downregulated the protein levels of the bone resorption marker (receptor activator of nuclear factor-κB ligand), while upregulated the levels of the bone formation markers (bone morphogenetic protein 2, runt-related transcription factor 2, alkaline phosphatase, and osteoprotegerin) in alveolar bone of the periodontitis rats. Hematoxylin and eosin, immunohistochemical staining, and Western blot analysis indicated that YNJ attenuated the inflammation and decreased the levels of interleukin-6 and tumor necrosis factor-α in the alveolar bone. In addition, a total of 61 compounds were identified from YNJ. Network pharmacology indicated that the nucleotide binding oligomerization domain-like receptor signaling pathway was the main pathway for YNJ in the treatment of periodontitis. The experiments confirmed that YNJ administration inhibited LPS induced-pyroptosis in alveolar bone through suppressing the phosphorylation of nuclear factor κB, reduced expression of NOD-like receptor family pyrin domain containing 3, and Caspase-1, subsequently suppressing the interleukin-1β secretion., Conclusion: YNJ is an effective therapeutic strategy for periodontitis and acts by inhibiting pyroptosis and NFκB/NLRP3/IL-1β pathway in alveolar bone., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

We aimed to characterize the association between air pollutants exposure and periodontal diseases outpatient visits and to explore the interactions between ambient air pollutants and meteorological factors. The outpatient visits data of several large stomatological and general hospitals in Hefei during 2015-2020 were collected to explore the relationship between daily air pollutants exposure and periodontal diseases by combining Poisson's generalized linear model (GLMs) and distributed lag nonlinear model (DLNMs). Subgroup analysis was performed to identify the vulnerability of different populations to air pollutants exposure. The interaction between air pollutants and meteorological factors was verified in both multiplicative and additive interaction models. An interquartile range (IQR) increased in nitrogen dioxide (NO 2 ) concentration was associated with the greatest lag-specific relative risk (RR) of gingivitis at lag 3 days (RR = 1.087, 95% CI 1.008-1.173). Fine particulate matter (PM 2.5 ) exposure also increased the risk of periodontitis at the day of exposure (RR = 1.049, 95% CI 1.004-1.096). Elderly patients with gingivitis and periodontitis were both vulnerable to PM 2.5 exposure. The interaction analyses showed that exposure to high levels of NO 2 at low temperatures was related to an increased risk of gingivitis, while exposure to high levels of NO 2 and PM 2.5 may also increase the risk of gingivitis and periodontitis in the high-humidity environment, respectively. This study supported that NO 2 and PM 2.5 exposure increased the risk of gingivitis and periodontitis outpatient visits, respectively. Besides, the adverse effects of air pollutants exposure on periodontal diseases may vary depending on ambient temperature and humidity., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background and Purpose: Low-grade inflammation, a common feature of both diabetes and periodontitis, partly accounts for the complexity and refractoriness of diabetes-associated periodontitis. Adiponectin (APN), the most abundant adipokine in human blood, has been widely reported to have anti-inflammatory functions. Herein, we investigated the ability of an APN receptor agonist, AdipoAI, to alleviate diabetes-associated periodontitis. Furthermore, we revealed the possible mechanism underlying its anti-inflammatory effects., Experimental Approach: The maxillary first molar of Zucker diabetic fatty (ZDF) rats was ligated to construct a diabetes-associated periodontitis model, and rats were administered AdipoAI by gavage. We examined diabetes-related indexes, pathological changes in insulin target organs, alveolar bone resorption and systemic and local inflammation. In vitro, transwell assays were used to evaluate monocyte/macrophage migration induced by human gingival fibroblasts (hGFs) with/without AdipoAI treatment. Additionally, we examined chemokine expression levels in hGFs and hGF-induced monocyte/macrophage migration upon siRNA knockdown of Adiponectin receptor expression. Expression of Adipo1/Adipo2 receptors and inflammation-related signalling pathways were examined by IHC and WB, followed by confirmation with an NF-κB P65 inhibitor (BAY 11-7082)., Key Results: AdipoAI lowered fasting blood glucose and serum insulin in ZDF rats and alleviated inflammation in insulin target tissues. Locally, AdipoAI reduced alveolar bone absorption and gingival inflammation. Mechanistically, AdipoAI inhibited hGF-induced monocyte/macrophage migration by reducing CCL2 secretion. In hGFs, AdipoAI attenuated LPS-induced activation of NF-κB P65 and CCL2 expression, which was dependent on the Adipo receptor 1., Conclusion and Implications: AdipoAI, with its ability to alleviate inflammatory damage in tissues, is a candidate for diabetes-associated periodontitis treatment., (© 2023 British Pharmacological Society.)

This joint report from the Italian Society of Orthopaedics and Traumatology (SIOT) and the Italian Society of Periodontology and Implantology (SIdP) aims for a consensus around the scientific rationale and clinical strategy for the management of osteoporotic patients affected by periodontitis who are undergoing anti-resorptive (AR) therapy to manage the risk of the occurrence of a medication-related osteonecrosis of the jaws (MRONJ). Osteoporosis and periodontitis are chronic diseases with a high prevalence in aging patients, and they share some of the same pathogenetic mechanisms based upon inflammation. Available evidence shows the relationship among osteoporosis, AR agents, periodontitis and implant therapy in relation to the incidence of MRONJ. Uncontrolled periodontitis may lead to tooth loss and to the need to replace teeth with dental implants. Tooth extraction and surgical dental procedures are recognized as the main risk factors for developing MRONJ in individuals taking AR therapy for osteometabolic conditions. Although the incidence of MRONJ in osteometabolic patients taking AR therapy may be as low as 0.9%, the increasing prevalence of osteoporosis and the high prevalence of periodontitis suggest that this potential complication should not be overlooked. Good clinical practice (GCP) guidelines are proposed that aim at a more integrated approach (prescriber, dentist, periodontist and dental hygienist) in the management of periodontitis patients undergoing AR therapy for osteometabolic disorders to reduce the risk of MRONJ. Dental professional and prescribers should educate patients regarding the potential risk associated with the long-term use of AR therapy and oral health behavior., (© 2023. The Author(s).)

Introduction: Excessive lipoperoxidation is accompanied by accumulation of peroxidation products and depletion of antioxidant re-serves, which cause hyperenzymemia and the accumulation of toxic substances. The level of endotoxicosis is determined by the content of hydrophilic and hydrophobic products in the blood., Aim: To define the pathogenetic role of endogenous intoxication in the dynamics of development of experimental periodontitis of bacterial-immune genesis., Materials and Methods: The experiment was conducted on rats. The animals were divided into three groups: group 1 - control group/intact; group 2 - model periodontitis at 7 days; group 3 - model periodontitis at 30 days. The experimental bacterial-immune periodon-titis was induced by injection into the tissue of the periodontal complex of the microorganisms' mixture diluted with egg's albumin. For the study, we selected the blood serum in which the content of middle molecular weight molecules and erythrocyte intoxication index were determined. The results were statistically analyzed by means of non-parametric indices methods., Results: The development of generalized periodontitis is characterized by the occurrence of oxidative stress, which leads to violation of the metabolism in the mucous membrane of the oral cavity resulting in the accumulation of toxic products and the development of endogenous intoxication. The results show that the content of middle molecular weight molecules (aromatic amino and chain amino acids) determined on day 7 of the experiment was 1.11 times higher than that of the control group (p<0.01) and by 1.16 times (p<0.01), respectively. Comparing the levels of the above hydrophilic components of endogenous intoxication at 30 days of experimental peri-odontitis, we found a probable increase in these indicators compared with those at 7 days of the experiment. Studying the level of eryth-rocyte intoxication index, we found that at 7 days of experimental periodontitis this index was 1.28 times higher (p<0.01) than that of the intact group and continued to increase at 30 days., Conclusions: The dynamics of experimental periodontitis of bacterial-immune genesis show that the highest rates of endogenous intoxication are found in the late stages of the dynamics of the inflammatory process in the periodontium, namely at 30 days of the experiment, which may indicate chronic inflammation., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Periodontitis is the most widespread oral disease and is closely related to the oral microbiota. The oral microbiota is adversely affected by some pharmacologic treatments. Systemic antibiotics are widely used for infectious diseases but can lead to gut dysbiosis, causing negative effects on the human body. Whether systemic antibiotic-induced gut dysbiosis can affect the oral microbiota or even periodontitis has not yet been addressed. In this research, mice were exposed to drinking water containing a cocktail of four antibiotics to explore how systemic antibiotics affect microbiota pathogenicity and oral bone loss. The results demonstrated, for the first time, that gut dysbiosis caused by long-term use of antibiotics can disturb the oral microbiota and aggravate periodontitis. Moreover, the expression of cytokines related to Th17 was increased while transcription factors and cytokines related to Treg were decreased in the periodontal tissue. Fecal microbiota transplantation with normal mice feces restored the gut microbiota and barrier, decreased the pathogenicity of the oral microbiota, reversed the Th17/Treg imbalance in periodontal tissue, and alleviated alveolar bone loss. This study highlights the potential adverse effects of long-term systemic antibiotics-induced gut dysbiosis on the oral microbiota and periodontitis. A Th17/Treg imbalance might be related to this relationship. Importantly, these results reveal that the periodontal condition of patients should be assessed regularly when using systemic antibiotics in clinical practice., (© 2022. The Author(s).)

Statement of Problem: The outcome of implant-supported fixed complete dentures in edentulous patients with a history of periodontitis is unclear., Purpose: The purpose of this retrospective clinical study was to assess the clinical outcomes of immediate loaded fixed complete dentures in individuals with a history of periodontitis and to analyze risk factors related to implant failure., Material and Methods: A total of 642 implants (146 prostheses) in 119 patients were included. The follow-up period ranged from 2 to 7 years. Implant survival rates, marginal bone loss, mechanical complications, biologic complications, and patient satisfaction were evaluated. The Pearson chi-square test, independent samples t test, and multivariate generalized estimating equation were performed for statistical analysis (α=.05)., Results: Eleven implants in 9 patients failed, leading to overall survival rates of 98.3% at the implant level and 92.4% at the patient level. The mean ±standard deviation marginal bone loss was 0.62 ±0.86 mm, and marginal bone loss did not differ significantly between axial and tilted implants (P>.05). Mechanical complications were detected in 55 (37.7%) definitive prostheses; biologic complications were detected in 318 (49.5%) implants. Smokers had a significantly lower survival rate than nonsmokers (odds ratio: 6.880, P=.013). Bruxers had a significantly higher incidence of mechanical complications than nonbruxers (P<.001)., Conclusions: The immediate loaded fixed complete denture supported by implants is a suitable treatment option for edentulous patients with a history of periodontitis, with high survival implant rates. Smoking is a risk factor for implant failure. Bruxism may increase the incidence of mechanical complications with implant-supported fixed complete dentures, and the overall biologic complication incidence is comparatively high., (Copyright © 2022 Editorial Council for The Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aimed to investigate the relationship between dental metal allergy, periodontitis, and palmoplantar pustulosis among patients from a dental metal allergy clinic over a period of 8 years., Methods: This study included 436 patients who visited our dental metal allergy clinic between April 1, 2009 and March 31, 2016. Diagnoses of skin diseases, periodontal records, dental metal series patch test results, and electron probe microanalysis (EPMA) data were obtained from medical records. Relative risk (RR) values were estimated from these data., Results: Of the 359 patients who underwent the patch test, 241 showed a positive reaction. Of the 187 patients who underwent EPMA, 113 had allergenic metals in their dental prostheses. These patients were suspected to have a dental metal allergy. Furthermore, 150 of the 436 patients were diagnosed with palmoplantar pustulosis (PPP). The RR of metal allergy between patients with PPP and healthy subjects was 3.88. The RR of periodontal disease between patients with PPP and PPP-negative patients in the national average was 2.54., Conclusion: In this study, both dental metal allergy and periodontitis showed a high RR for PPP.

Aim This study aimed to compare the long-term outcome of implant therapy in partially edentulous patients with severe periodontitis compared to those with no history of periodontitis.Design Retrospective cohort study.Cohort selection Eighty-eight patients (34 men and 54 women; age ranging from 28 to 45 years) with severe periodontitis (47 patients with 108 implants) and no history of periodontitis (41 patients with 78 implants) were included in this institutional study. All these cohorts had received implants 6-8 years previously.Data analysis Probing pocket depth, radiographic marginal bone level and peri-implantitis were the primary outcomes, while bleeding on probing was the secondary outcome. The effect of variables was measured by odds ratio with 95% confidence interval. Both patient-level and implant-level analyses were used to evaluate the association between peri-implantitis and potential risk factors. In addition, the association between probing pocket depth and radiographic marginal bone level with potential risk factors was assessed at implant-level analyses. In contrast, for patient-level data, a positive relationship was assessed with the Chi-square test.Results Patients with a history of severe periodontitis (OR = 11.13; p = 0.045), implants with a lack (<2 mm) of peri-implant keratinised mucosa (OR = 14.94; p <0.001) and implants placed in bone-grafted sites (OR = 4.93; p = 0.047) were associated with greater risk of peri-implantitis, at 6-8 years post-implant placement. The risk of developing radiographic marginal bone level ≥3 mm was significantly greater (OR = 1.20; p <0.001) in patients with higher full-mouth bleeding scores. The chance of peri-implant bleeding on probing was independently and especially higher in patients who brushed their teeth at most once per day (OR = 3.20; p = 0.04), with higher full-mouth bleeding score values (OR = 1.16; p <0.001) and irregular recall visits (OR = 15.34; p = 0.001).Conclusion This retrospective cohort study concluded that partially edentulous patients with a history of severe periodontitis were more prone to develop peri-implantitis at 6-8 years post-implant placement., (© 2022. The Author(s), under exclusive licence to the British Dental Association.)

Oral and gum health have long been associated with incidence and outcomes of cardiovascular disease. Periodontal disease increases myocardial infarction (MI) mortality by sevenfold through mechanisms that are not fully understood. The goal of this study was to evaluate whether lipopolysaccharide (LPS) from a periodontal pathogen accelerates inflammation after MI through memory T-cell activation. We compared four groups [no MI, chronic LPS, day 1 after MI, and day 1 after MI with chronic LPS (LPS + MI); n = 68 mice] using the mouse heart attack research tool 1.0 database and tissue bank coupled with new analyses and experiments. LPS + MI increased total CD8 + T cells in the left ventricle versus the other groups ( P < 0.05 vs. all). Memory CD8 + T cells (CD44  +  CD27 + ) were 10-fold greater in LPS + MI than in MI alone ( P = 0.02). Interleukin (IL)-4 stimulated splenic CD8 + T cells away from an effector phenotype and toward a memory phenotype, inducing secretion of factors associated with the Wnt/β-catenin signaling that promoted monocyte migration and decreased viability. To dissect the effect of CD8 + T cells after MI, we administered a major histocompatibility complex-I-blocking antibody starting 7 days before MI, which prevented effector CD8 + T-cell activation without affecting the memory response. The reduction in effector cells diminished infarct wall thinning but had no effect on macrophage numbers or MertK expression. LPS + MI + IgG attenuated macrophages within the infarct without effecting CD8 + T cells, suggesting these two processes were independent. Overall, our data indicate that effector and memory CD8 + T cells at post-MI day 1 are amplified by chronic LPS to potentially promote infarct wall thinning. NEW & NOTEWORTHY Although there is a well-documented link between periodontal disease and heart health, the mechanisms are unclear. Our study indicates that in response to circulating periodontal endotoxins, memory CD8 + T cells are activated, resulting in an acceleration of macrophage-mediated inflammation after MI. Blocking activation of effector CD8 + T cells had no effect on the macrophage numbers or wall thinning at post-MI day 1 , indicating that this response was likely due in part to memory CD8 + T cells.

Periodontitis is an inflammatory disease associated with severe alveolar bone loss and is dominantly induced by lipopolysaccharide from Gram-negative bacteria; however, the role of Gram-positive bacteria in periodontal bone resorption remains unclear. In this study, we examined the effects of lipoteichoic acid (LTA), a major cell-wall factor of Gram-positive bacteria, on the progression of inflammatory alveolar bone loss in a model of periodontitis. In coculture of mouse primary osteoblasts and bone marrow cells, LTA induced osteoclast differentiation in a dose-dependent manner. LTA enhanced the production of PGE 2 accompanying the upregulation of the mRNA expression of mPGES-1, COX-2 and RANKL in osteoblasts. The addition of indomethacin effectively blocked the LTA-induced osteoclast differentiation by suppressing the production of PGE 2 . Using ex vivo organ cultures of mouse alveolar bone, we found that LTA induced alveolar bone resorption and that this was suppressed by indomethacin. In an experimental model of periodontitis, LTA was locally injected into the mouse lower gingiva, and we clearly detected alveolar bone destruction using 3D-μCT. We herein demonstrate a new concept indicating that Gram-positive bacteria in addition to Gram-negative bacteria are associated with the progression of periodontal bone loss.

Background: The aim of this study was to evaluate the role of AT1 and AT2 receptors in a periodontal inflammation experimental model., Methods: Periodontal inflammation was induced by LPS/ Porphyromonas gingivalis . Maxillae, femur, and vertebra were scanned using Micro-CT. Maxillae were analyzed histopathologically, immunohistochemically, and by RT-PCR., Results: The vertebra showed decreased BMD in AT1 H compared with WT H ( p < 0.05). The femur showed increased Tb.Sp for AT1 H and AT2 H, p < 0.01 and p < 0.05, respectively. The Tb.N was decreased in the vertebra (WT H-AT1 H: p < 0.05; WT H-AT2 H: p < 0.05) and in the femur (WT H-AT1 H: p < 0.01; WT H-AT2 H: p < 0.05). AT1 PD increased linear bone loss ( p < 0.05) and decreased osteoblast cells ( p < 0.05). RANKL immunostaining was intense for AT1 PD and WT PD ( p < 0.001). OPG was intense in the WT H, WT PD, and AT2 PD when compared to AT1 PD ( p < 0.001). AT1 PD showed weak immunostaining for osteocalcin compared with WT H, WT PD, and AT2 PD ( p < 0.001). AT1 H showed significantly stronger immunostaining for osteonectin in fibroblasts compared to AT2 H ( p < 0.01)., Conclusion: AT1 receptor knockout changed bone density, the quality and number of bone trabeculae, decreased the number of osteoblast cells, and increased osteonectin in fibroblasts.

Objective: To determine the crosstalk of osteogenesis and osteoclastogenesis of alveolar bone in lipopolysaccharide (LPS)-induced periodontitis in mice., Methods: A representative periodontitis model was established by treating mice with LPS, and osteoblasts and osteoclasts were cultured. Osteoblasts and osteoclasts were cocultured to determine the effects of LPS on the crosstalk of osteogenesis and osteoclastogenesis. Quantitative polymerase chain reaction (qPCR) was performed to determine the expression of osteoclastogenesis makers underlying the potential mechanisms., Results: The morphological and pathological changes in alveolar bone were observed in LPSinduced mice and LPS dose-dependently suppressed osteogenesis. The mRNA expression of cathepsin K, as a marker of osteoclasts, was accordingly downregulated in the coculture. The mRNA expression of osteoprotegerin was increased, while that of receptor activator of nuclear factor-κB ligand (RANKL) was decreased with an increased concentration of LPS. Moreover, the mRNA expression of toll-like receptor 4 (TLR4) was upregulated by LPS, whereas TLR4 knockout partially recovered osteoclast differentiation in the upper layer of the coculture., Conclusion: LPS dose-dependently suppressed osteogenesis but had a bidirectional effect on osteoclastogenesis. The combined effects of LPS on osteogenesis, osteoclastogenesis and their crosstalk via TLR4 account for alveolar bone loss in periodontitis.

Bacterial infection caused cell pyroptosis and gingival inflammation contributes to periodontitis progression, and lipopolysaccharide (LPS) is the main infectious agent of gram-negative bacteria, which is reported to be closely associated with gingival inflammation and periodontitis. In this study, the primary human periodontal ligament cells (PDLCs) were isolated, cultured, and exposed to LPS treatment, and the results suggested that LPS suppressed cell viability and promoted pro-inflammatory cytokines' (IL-1β, IL-18, IL-6, and TNF-α) generation and secretion in the PDLCs and its supernatants in a time- and concentration-dependent manner. Also, we noticed that LPS upregulated NLRP3, Gasdermin D, and cleaved caspase-1 to trigger pyroptotic cell death in the PDLCs. Further experiments identified that glycogen synthase kinase-3β (GSK-3β) was upregulated by LPS treatment, and inhibition of GSK-3β by its inhibitor (GSKI) or GSK-3β downregulation vectors was effective to restore normal cellular functions in LPS-treated PDLCs. Mechanistically, blockage of GSK-3β restrained NLRP3-meidated cell pyroptosis and inflammation, resulting in the recovery of cell viability and inhibition of cell death in PDLCs treated with LPS, which further ameliorated periodontitis progression. Finally, we collected the serum from periodontitis patients and healthy volunteers, and the clinical data supported that those pro-inflammatory cytokines were also upregulated in patients' serum but not in the healthy participants. Taken together, we concluded that targeting the GSK-3β/NLRP3 pathway mediated cell pyroptosis was effective to attenuate LPS-induced cell death and inflammation in PDLCs, and this study firstly investigated this issue, which broadened our knowledge in this field.

It was hypothesized that periodontal diseases could be influenced by nutrition and food types. However, the role of nutritional factors in the risk of periodontal disease has not been clearly elucidated. This study was aimed at investigating the relationship between coffee, green tea, or soft drink intake and periodontitis. This prospective cohort study used epidemiological data from 2004 to 2016 from the Korean Genome and Epidemiology Study. Among 173,209 participants, 9,933 with periodontitis and 124,922 controls were selected. The frequency histories of coffee/green tea/soft drink intake among the participants were analyzed, and intake was categorized as no drink, mild drink (one time a month through six times a week), and heavy drink (one or more times a day). Variable factors were adjusted using logistic regression analysis (adjusted model). The chi-square test and independent t -test were used for statistical analysis. Adjusted odds ratio (aOR) for coffee or green tea intake and periodontitis were not statistically significant. The aOR was 1.16 (95% confidence interval (CI) = 1.11-1.21, P < 0.001) for mild soft drink intake and 1.02 (95%CI = 0.96-1.09, P = 0.518) for heavy soft drink intake. Subgroup analysis showed that mild soft drink intake was significant across all groups ( P < 0.05), whereas coffee and green tea intakes were not significant in any subgroup. Overall, the study elucidated an association between mild soft drink intake and periodontitis., Competing Interests: The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2021 Seok Jin Hong et al.)

Periodontitis is usually sustained from microorganism of oral cavity, like Porphyromonas gingivalis ( P. gingivalis ). Periodontal disease is an infectious disease that afflicts a large number of people. Researches are investigating on the mesenchymal stem cells (MSCs) response to inflammatory events in combination with antioxidant substances. In particular, ascorbic acid (AA) increased cell proliferation, upregulated the cells pluripotency marker expression, provide a protection from inflammation, and induced the regeneration of periodontal ligament tissue. The purpose of the present research was to investigate the effects of AA in primary culture of human periodontal ligament stem cells (hPDLSCs) exposed to P. gingivalis lipopolysaccharide (LPS-G). The effect of AA on hPDLSCs exposed to LPS-G was determined through the cell proliferation assay. The molecules involved in the inflammatory pathway and epigenetic regulation have been identified using immunofluorescence and Western blot analyses. miR-210 level was quantified by qRT-PCR, and the ROS generation was finally studied. Cells co-treated with LPS-G and AA showed a restoration in terms of cell proliferation. The expression of NF κ B, MyD88, and p300 was upregulated in LPS-G exposed cells, while the expression was attenuated in the co-treatment with AA. DNMT1 expression is attenuated in the cells exposed to the inflammatory stimulus. The level of miR-210 was reduced in stimulated cells, while the expression was evident in the hPDLSCs co-treated with LPS-G and AA. In conclusion, the AA could enhance a protective effect in in vitro periodontitis model, downregulating the inflammatory pathway and ROS generation and modulating the miR-210 level., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Guya D. Marconi et al.)

Objective: The aim: To study the content of trace elements (cadmium and zinc) in the blood and oral fluid in people with generalized periodontitis and work and live permanently in adverse environmental conditions., Patients and Methods: Materials and methods: In order to study the prevalence of periodontal diseases in adults living in areas with high level of soil contamination with heavy metal salts and working in the workplace with occupational hazards, there were studied 163 people who did not have somatic diseases, namely: 133 employees of Burshtyn Thermal Power Plant (TPP) and 30 persons who do not work at Burshtyn TPP., Results: Results: The results of biochemical examination of blood and oral fluid in persons with generalized periodontitis of the I, II degree of severity and being exposed to adverse environmental factors, show changes in the trace element spectrum of blood and oral fluid, namely: a decrease in amount of zinc and an increase in amount of cadmium, which may indicate the disorder of microelement metabolism under conditions of chronic influence of small doses of salts of heavy metals., Conclusion: Conclusions: As a result of the performed study, a violation of micronutrient metabolism in biological fluids (blood and oral fluid) was found in persons exposed to adverse environmental factors.

Periodontitis is a widespread oral disease that results in the loss of alveolar bone. Low-intensity pulsed ultrasound (LIPUS), which is a new therapeutic option, promotes alveolar bone regeneration in periodontal bone injury models. This study investigated the protective effect of LIPUS on oxidative stress in periodontitis and the mechanism underlying this process. Methods: An experimental periodontitis model was induced by administering a ligature . Immunohistochemistry was performed to detect the expression levels of oxidative stress, osteogenic, and osteoclastogenic markers in vivo . Cell viability and osteogenic differentiation were analyzed using the Cell Counting Kit-8, alkaline phosphatase, and Alizarin Red staining assays. A reactive oxygen species assay kit, lipid peroxidation MDA assay kit, and western blotting were used to determine oxidative stress status in vitro . To verify the role of nuclear factor erythroid 2-related factor 2 (Nrf2), an oxidative regulator, during LIPUS treatment, the siRNA technique and Nrf2 -/- mice were used. The PI3K/Akt inhibitor LY294002 was utilized to identify the effects of the PI3K-Akt/Nrf2 signaling pathway. Results: Alveolar bone resorption, which was experimentally induced by periodontitis in vivo , was alleviated by LIPUS via activation of Nrf2. Oxidative stress, induced via H 2 O 2 treatment in vitro , inhibited cell viability and suppressed osteogenic differentiation. These effects were also alleviated by LIPUS treatment via Nrf2 activation. Nrf2 silencing blocked the antioxidant effect of LIPUS by diminishing heme oxygenase-1 expression. Nrf2 -/- mice were susceptible to ligature-induced periodontitis, and the protective effect of LIPUS on alveolar bone dysfunction was weaker in these mice. Activation of Nrf2 by LIPUS was accompanied by activation of the PI3K/Akt pathway. The oxidative defense function of LIPUS was inhibited by exposure to LY294002 in vitro . Conclusions: These results demonstrated that LIPUS regulates alveolar bone homeostasis in periodontitis by attenuating oxidative stress via the regulation of PI3K-Akt/Nrf2 signaling. Thus, Nrf2 plays a pivotal role in the protective effect exerted by LIPUS against ligature-induced experimental periodontitis., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Periodontitis is a multifactorial inflammatory disease of tooth supporting tissues caused by oral biofilms, influenced by environmental and genetic factors, among others. Ethanol consumption has been considered a factor that enhances alveolar bone loss, especially in high doses. The present study aims to investigate the changes promoted by ethanol binge drinking per se or associated with ligature-induced periodontal breakdown on alveolar bone loss., Materials and Methods: Thirty-two Wistar rats were randomly allocated into four groups: control (C), ethanol (3g/kg/day; 3 days On-4 days Off protocol by gavage for 28 days, EtOH), experimental periodontitis (EP) and experimental periodontitis plus ethanol administration (EP+EtOH). On day 14th, periodontitis was induced by ligatures that were placed around the lower first molars. On day 28th, the animals were euthanized and mandibles were submitted to stereomicroscopy for exposed root area analysis and micro-computed tomography (micro-CT) for the evaluation of alveolar bone loss and microstructural parameters., Results: The results revealed that ligature-induced alveolar bone loss is aggravated by ethanol binge drinking compared to controls (1.06 ± 0.10 vs 0.77 ± 0.04; p<0.0001). In addition, binge drinking per se altered the alveolar bone quality and density demonstrating a reduction in trabecular thickness, trabecular number parameter and bone density percentual. Periodontal disorder plus ethanol binge drinking group also demonstrated reduction of the quality of bone measured by trabecular thickness., Conclusions: In conclusion, intense and episodic ethanol intake decreased alveolar bone quality in all microstructural parameters analyzed which may be considered a modifying factor of periodontitis, intensifying the already installed disease., Competing Interests: The authors have declared that no competing interests exist.

Background: Mutation of the gene for acid sphingomyelinase (ASMase) causes Niemann-Pick disease. However, the effect of ASMase deficiency on periodontal health is unknown. Periodontal disease is a disease resulting from infection and inflammation of periodontal tissue and alveolar bone that support the teeth. The goal of this study was to determine the role of ASMase deficiency in periodontal inflammation and alveolar bone loss., Methods: We induced periodontitis in wild-type and ASMase-deficient (ASMase -/- ) mice with periodontal lipopolysaccharide (LPS) injection and compared the alveolar bone loss and periodontal inflammation between these mice., Results: Results showed that ASMase deficiency did not significantly change metabolic parameters, but exacerbated LPS-induced alveolar bone loss, osteoclastogenesis, and periodontal tissue inflammation. To understand the mechanisms by which ASMase deficiency aggravates LPS-induced periodontitis, we analyzed sphingolipids in periodontal tissues. Results showed that ASMase deficiency led to increases in not only sphingomyelin, but also ceramide (CER), a bioactive sphingolipid known to promote inflammation. Results further showed that ASMase deficiency increased CER de novo synthesis., Conclusion: ASMase deficiency exacerbated LPS-induced alveolar bone loss and periodontal inflammation. ASMase deficiency leads to an unexpected CER increase by stimulating de novo synthesis CER, which is likely to be involved in the ASMase deficiency-exacerbated periodontitis., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA.)

It can be difficult to identify health/functional foods that exert therapeutic benefits for alleviating gingivitis and periodontitis. Recently, extracts of Boesenbergia pandurata (Roxb.), which is a tropical plant, have shown promising inhibitory activity against lipopolysaccharide-induced periodontitis. As a result, a clinical trial is being planned to assess utility of B. pandurata (Roxb.) extracts for promoting oral health; this study was designed to determine an appropriate human dose of the extracts for the trial. Pharmacokinetic studies of panduratin A, which is an active substance in fingerroot, were carried out in mice, rats, and dogs after oral administration of the extracts. The clearance data for each species were used to estimate clearance in humans through allometric scaling based on the maximum lifespan potential, and a daily dose providing sufficient anti-periodontitis activity was estimated for use in the clinical trial. The findings indicated that allometric scaling is a reasonable approach that is relatively free of safety issues and can be used to determine doses of substances for incorporation into health/functional foods appropriate for humans.

Periodontitis is the leading cause of adult tooth loss, and those who smoke are at an increased risk of developing periodontitis. α7 nicotinic acetylcholine receptor (α7 nAChR) is proposed to mediate the potential synergistic effect of nicotine and inflammation in smoking-related periodontitis. However, this has not been experimentally demonstrated. We isolated and cultured human periodontal ligament stem cells (PDLSCs) from healthy and inflamed tissues. PDLSCs were treated with either inflammatory factors or nicotine. We measured expression of genes that are associated with osteogenic differentiation and osteoclast formation using RT-qPCR and Western blot analyses. Besides, immunohistochemical staining, micro-CT analysis and tartaric acid phosphatase staining were used to measure α7 nAChR expression and function. Inflammation up-regulated α7 nAChR expression in both periodontal ligament tissues and PDLSCs. The up-regulated α7 nAChR contributed to the synergistic effect of nicotine and inflammation, leading to a decreased capability of osteogenic differentiation and increased capability of osteoclast formation-induction of PDLSCs. Moreover, the inflammation-induced up-regulation of α7 nAChR was partially dependent on the level of phosphorylated GSK-3β. This study provides experimental evidence for the pathological development of smoking-related periodontitis and sheds new light on developing inflammation and α7 nAChR-targeted therapeutics to treat and prevent the disease., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: Although the immunomodulatory properties of calcitriol in bone metabolism have been documented for decades, its therapeutic role in the management of periodontitis remains largely unexplored. In this study, we hypothesized that calcitriol suppresses lipopolysaccharide (LPS)-induced alveolar bone loss by regulating T helper (Th) cell subset polarization., Methods: To test this hypothesis, we determined the effect of calcitriol intervention on the development of LPS-induced periodontitis in rats in terms of bone loss (micro-CT analysis), local inflammatory infiltration levels, the number of osteoclasts (hematoxylin and eosin staining) and the level of osteoclastogenesis (tartrate-resistant acid phosphatase method). Furthermore, immunohistochemistry was used to assess the expression levels of the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) as well as the cytokine levels of interferon-γ (IFN-γ), interleukin-4 (IL-4), IL-17, and IL-10 throughout the LPS-injected region. Finally, the polarization potential of Th cells in peripheral blood was analyzed using flow cytometry., Results: Calcitriol intervention decreased alveolar bone loss in response to LPS injection and inflammatory cell infiltration. Analysis of osteoclast number and RANKL and OPG expression showed that bone resorption activity was largely suppressed in response to calcitriol administration, along with decreased IL-17 levels but increased IL-4 and IL-10 levels in periodontal tissues (the LPS-injected region). Similarly, the percentages of Th2 and Treg cells in peripheral blood increased, but the percentages of Th1 and Th17 cells decreased in rats receiving calcitriol., Conclusion: Our findings suggest that calcitriol can be used to inhibit bone loss in experimental periodontitis, likely via the regulation of local and systemic Th cell polarization., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Periodontitis is an important public health concern worldwide. Because rodents from the genus Rattus are resistant to spontaneous periodontitis, experimental periodontitis must be initiated by mechanical procedures and interventions. Due to their exacerbated Th1 response and imbalanced Th17 regulatory T-cell responses, Lewis rats are highly susceptible to inducible inflammatory and autoimmune diseases. We hypothesized that feeding Lewis rats a diet high in sucrose and casein (HSC) would alter the oral microenvironment and induce inflammation and the development of periodontitis lesions without mechanical intervention. A baseline group (BSL, n = 8) was euthanized at age 6 wk. Beginning at 6 wk of age, 2 groups of Lewis rats were fed standard (STD, n = 12) or HSC ( n = 20) chow and euthanized at 29 wk of age. We evaluated the degree of periodontitis through histology and μCT of maxillae and mandibles. The HSC-induced inflammatory response of periodontal tissues was assessed by using immunohistochemistry. Gene expression analysis of inflammatory cytokines associated with Th1 and Th17 responses, innate immunity cytokines, and tissue damage in response to bacteria were assessed also. The potential systemic effects of HSC diet were evaluated by assessing body composition and bone densitometry endpoints; serum leptin and insulin concentrations; and gene expression of inflammatory cytokines in the liver. Placing Lewis rats on HSC diet for 24 wk induced a host Th1-immune response in periodontal tissues and mild to moderate, generalized periodontitis characterized by inflammatory cell infiltration (predominantly T cells and macrophages), osteoclast resorption of alveolar bone, and hyperplasia and migration of the gingival epithelium. HSC-fed Lewis rats developed periodontitis without mechanical intervention in the oral cavity and in the absence of any noteworthy metabolic abnormalities. Consequently, the rat model we described here may be a promising approach for modeling mild to moderate periodontitis that is similar in presentation to the human disease.

This study tested whether microRNA (miR)-200c can attenuate the inflammation and alveolar bone resorption in periodontitis by using an in vitro and a rat model. Polyethylenimine (PEI) was used to facilitate the transfection of plasmid DNA encoding miR-200c into primary human gingival fibroblasts (HGFs) and gingival tissues of rats. We first analyzed how proinflammatory and osteoclastogenic mediators in HGFs with overexpression of miR-200c responded to Porphyromonas gingivalis lipopolysaccharide (LPS-PG) challenge in vitro. We observed that overexpression of miR-200c significantly reduced interleukin (IL)-6 and 8 and repressed interferon-related developmental regulator-1 (IFRD1) in HGFs. miR-200c also downregulated p65 and p50 . In a rat model of periodontitis induced by an LPS injection at the gingival sulcus of the second maxillary molar (M2), we analyzed how the mediators in rat gingiva and alveolar bone resorption responded to miR-200c treatment by a local injection of PEI-plasmid miR-200 nanoplexes. We observed that the local injection of miR-200c significantly upregulated miR-200c expression in gingiva and reduced IL-6, IL-8, IFRD1 , and the ratio of receptor activator of nuclear factor kappa-B ligand/osteoprotegerin. Using micro-computed tomography analysis and histomorphometry, we further confirmed that local treatment with miR-200c effectively protected alveolar bone resorption in the rat model of periodontitis by reducing the distance between the cemento-enamel junction and the alveolar bone crest and the inter-radicular space in the upper maxilla at M2. These findings imply that miR-200c may serve as a unique means to prevent periodontitis and associated bone loss.

Periodontitis is an infectious disease characterized by chronic inflammation and progressive destruction of periodontal tissues. Chronic inflammatory environment may affect immunomodulatory function of periodontal ligament stem cells (PDLSCs) and promote shift toward proinflammatory phenotype contributing to propagation of periodontitis. Therefore, suppression of inflammatory response in PDLSCs represents a novel therapeutic approach. Extracellular vesicles (EVs) have been shown to display anti-inflammatory and immunosuppressive actions in different tissues and could represent a potent therapeutic tools against chronic inflammation during periodontitis. In the present study, we investigated the effects of EVs on the basal and lipopolysaccharide (LPS)-induced activity of NFκB signaling pathway in PDLSCs. We also examined the impact of EVs on the osteogenic differentiation and expression of osteogenesis-related genes. EVs were purified by differential ultracentrifugation from PDLSCs grown on gelatin-coated alginate microcarriers in a bioreactor. NFκB reporter assays demonstrated that EVs permanently suppressed basal and LPS-induced activity of NFκB in PDLSCs. Combined treatment with EVs and anti-TLR4 antibody (Ab) resulted in attenuation of the inhibitory effect on the NFκB activity, suggesting a possible interference through a competition for TLR4 signaling pathway. EVs also increased phosphorylation of Akt and its downstream target GSK3β (Ser 9) indicating that PI3K/Akt signaling pathway may act as suppressor of NFκB activity. LPS stimulated osteogenic mineralization of PDLSCs. Unexpectedly, anti-TLR4 blocking Ab per se significantly decreased osteogenic mineralization of PDLSCs. EVs did not affect osteogenic mineralization, but partially suppressed inhibitory effect of anti-TLR4 blocking Ab. Gene expression studies revealed significant effects of EVs on osteogenesis-related genes and possible interference with TLR4 signaling in PDLSCs. In conclusion, our study demonstrates that EVs suppress basal and LPS-induced activity of NFκB signaling pathway in PDLSCs and could potentially be used for targeting of chronic inflammation during periodontitis.

This study evaluated the arthritogenic effect of lipopolysaccharide (LPS) in a mouse model of periodontal disease. Periodontitis was induced in wild-type CD1 mice by nine LPS injections (10 or 50 ng) into the maxillary mucosa. Untreated mice or injected with LPS at the tail were used as controls. Two weeks after final inoculation, mice were sacrificed to collect blood, maxilla, and paw samples. Development and progression of periodontitis and arthritis were monitored using clinical assessment, micro-computed tomography (micro-CT), ultrasound (US), and histological analysis. CXCL1, IL-1β, IL-6, TNF-α, and anti-citrullinated peptide antibodies (ACPA) serum levels were determined by enzyme immunoassay. Ankle swelling and inflammation manifested after the 5th periodontal injection of 50 ng of LPS and progressed until the end of experiments. Periodontal injection of 10 ng of LPS and LPS tail injection did not induce paw changes. Therefore, the subsequent assessments were conducted only in mice periodontally injected with 50 ng of LPS. Maxillary micro-CT and histological analysis showed that LPS-induced alveolar bone resorption and vascular proliferation in periodontal tissue, but not inflammation. US and histology revealed increased joint space, leukocyte infiltration, synovial proliferation, and mild cartilage and bone destruction in the paws of mice orally injected. Cytokines and ACPA showed a trend towards an increase in LPS mice. This study shows that arthritis and periodontal disease can co-occur in wild-type mice after periodontal injection of LPS at optimal dose. Our model may be useful to improve the understanding of the mechanisms linking periodontitis and arthritis.

Background: Oral contraceptives pills (OCPs) are common and a convenient form of contraception. The use of hormonal contraceptives by women has been considered to influence gingival and periodontal disease progression., Aim: This study was conducted to assess the effect of oral contraceptive pills on the periodontal health., Materials and Method: A cross-sectional comparative study was conducted among 200 females aged 18 years and above of Jaipur city. The study subjects were divided into two groups i.e. contraceptive users and non-contraceptive users, each group consisted 100 females. Data was collected using Modified WHO Performa (1997). Periodontal status was examined using Community Periodontal Index (CPI) and Loss of Attachment (LOA). Chi-square test and one sample t-test was used for statistical analysis and P value was set (p< 0.05) as significant., Results: Mean CPI score in subjects and non-contraceptive users was 2.34+ 0.81 and 1.16+ 0.89 respectively. Mean LOA score in each group was 0.28+ 0.45 and 0.19+ 0.50 respectively., Conclusion: Oral Contraceptive pills had adverse effects on periodontal health.

Objective: The aim of this investigation was to determine the circulating levels of amyloid beta (Aβ) peptides using the Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS) model to induce periodontitis., Methods: Experimental periodontitis was induced in 6 male Sprague-Dawley rats. Alveolar bone loss was measure by micro computed tomography. Serum concentrations of Aβ 1-40 and Aβ 1-42 prior to periodontal induction, at 24 h, 7, 14, and 21 days the last injection of Pg-LPS., Results: The distance between the cemento-enamel junction and the bone crest (i.e., alveolar bone loss) was significantly higher at the end of periodontal induction compared to baseline (2.92 ± 0.29 mm vs. 3.8 ± 0.28 mm, P < 0.001). Periodontitis evoked a slight acute elevation of Aβ 1-40 serum levels that were maintained during the whole experiment. Aβ 1-42 peptide levels peak at the end of the study. A positive strong correlation was observed between alveolar bone loss and Aβ 1-40 serum levels at 7 days (r = 0.695, P = 0.012) and as well as with serum Aβ 1-42 concentrations at 21 days (r = 0.968, P = 0.002)., Conclusions: Periodontitis induced Pg-LPS produced increased serum levels of Aβ peptides. Further studies are needed to confirm our results and to investigate the mechanisms by which periodontitis could be associated with an overexpression of Aβ., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The purpose of the experimental study was to study the activity of lipid peroxidation and antioxidant systems in animals of different ages with experimental periodontitis with altered reactivity. Experiments were carried out on 30 non-linear white rats aged 2 months, which were divided into three groups: Group I - 10 animals with a hypoergic reaction, which was modeled by the administration of cyclophosphamide; Group II - 10 animals with hyper-hypergly reaction, which was modeled by administration of pyrogenal; Group III - 10 animals with normal reaction - a control group, which was intramuscularly injected with 1 ml of saline. Blood sampling and killing of animals were performed under thiopental anesthesia 7 days after the start of the experiment. In the blood serum, the content of diene conjugates, thiobarbituric oxidative active products, reduced glutathione, ceruloplasmin and catalase activity were determined by spectrophotometric method. In modeling hypoergic and hyperergic periodontitis, lipid peroxidation was activated with an increase in its initial products. The activity of the antioxidant system tended to decrease both in the hyperergic and hypoergic periodontitis in prepubertal animals, while at the same time there was a tendency to increase in adults. The data obtained indicate certain differences in the processes of lipid peroxidation and antioxidant protection in animals of different ages, which should be taken into account when extrapolating the data obtained in the clinic.

Context: Shikonin (SHI), an active component extracted from Radix Arnebiae, has been reported to possess anti-inflammatory properties in various cells. However, its effect on lipopolysaccharide (LPS)-stimulated human periodontal ligament cells (hPDLCs) is unknown., Objective: To investigate the effects of SHI on the expression of inflammatory related cytokines in LPS-stimulated hPDLCs., Materials and Methods: The effects of SHI (0.125, 0.25, 0.5, 1, and 2 μg/mL) on hPDLCs proliferation for 1, 3 and 7 days were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of interleukin-1 (IL-1), IL-6, tumor necrosis factor-α (TNF-α), matrix metalloproteinase-2 (MMP-2), MMP-9 and cyclooxygenase-2 (COX-2) were detected in hPDLCs following SHI treatment (0.25 and 0.5 μg/mL) using Quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR). The signaling pathways triggered by SHI in hPDLC were evaluated using western blotting., Results: LD50 of SHI is 1.7 μg/mL (day 1) and 1.1 μg/mL (day 3 and 7) in hPDLCs. No morphological changes were observed when hPDLCs were treated with LPS only (1 μg/mL) or LPS with SHI (0.25 and 0.5 μg/mL). Data from qRT-PCR suggests that SHI attenuates LPS-induced increases of IL-1, IL-6, TNF-α, MMP-2, MMP-9 and COX-2 in hPDLCs. Down-regulation of phosphorylated extracellular signal-regulated kinase (ERK) and nuclear factor-κB (NF-κB), and up-regulation of I-κB, were observed in LPS-stimulated hPDLCs after exposed to SHI at 0.25 or 0.5 μg/mL., Discussion and Conclusions: SHI possesses anti-inflammatory effects in LPS-stimulated hPDLCs via phospho-ERK and NF-κB/I-κB signaling pathways; this suggests that SHI may hold potential as an anti-inflammatory agent against periodontitis.

Periodontitis, which is a severe inflammatory disease caused by endotoxins secreted from oral pathogens, destructs gingival tissue and alveolar bone. Curcuma xanthorrhiza , commonly called Java turmeric, has been shown to possess anti-bacterial and anti-inflammatory activities. The present study evaluated the inhibitory effect of C. xanthorrhiza supercritical extract (CXS) standardized with xanthorrhizol on lipopolysaccharide (LPS)-induced periodontitis in an animal model. LPS was topically injected into the periodontium of Sprague-Dawley rats to induce periodontitis and CXS (30 and 100 mg·kg -1 ·day -1 ) was orally administered after day 12. Histologically, CXS inhibited the collapse of gingival tissue by preventing cell infiltration. CXS significantly downregulated the expression of matrix metalloproteases (MMPs) and inflammation-related biomarkers, such as nuclear factor-kappa B (NF-κB) and interleukin-1 beta (IL-1β) in gingival tissue. CXS also improved bone remodeling by downregulating osteoclastic transcription factors, such as nuclear factor of activated T-cells c1 (NFATc1), tartrate-resistant acid phosphatase (TRAP), and cathepsin K. In addition, CXS upregulated osteoblast differentiation-related markers, alkaline phosphate (ALP) and collagen type I alpha (COLA1). Thus, CXS can ameliorate periodontitis by inhibiting inflammation and improving bone remodeling.

The increased incidence of periodontal disease in recent years has garnered considerable attention. Numerous studies have confirmed that probiotics, such as lactic acid bacteria, can ameliorate periodontal inflammation. The current study aimed to assess the effect of an ethanol extract of Lactobacillus paracasei subsp. paracasei NTU 101-fermented skimmed milk (NTU101FM) on lipopolysaccharide (LPS)-induced periodontal inflammation in rats. NTU101FM ethanol extract significantly ameliorated the weight loss caused by periodontal inflammation. NTU101FM ethanol extract treatment also reduced the oral microbial levels and decreased the levels of alveolar bone loss. Finally, NTU101FM ethanol extract was found to ameliorate periodontal inflammation by decreasing the levels of pro-inflammatory cytokines and reducing oxidative stresses induced by LPS. Overall, our findings demonstrate that NTU101FM ethanol extract could be developed as a functional food that could ameliorate periodontal inflammation.

Objectives: This study aimed to establish lactate dehydrogenase (LDH) and β-glucuronidase as salivary biomarkers of periodontitis among smokers and non-smokers., Methods: This cross-sectional case-control study was conducted at the Aligarh Muslim University, Aligarh, India, between January and June 2017. A total of 200 participants were divided into four groups based on their periodontal and smoking statuses. Unstimulated mixed saliva samples were collected to estimate LDH and β-glucuronidase levels. In addition, total protein was estimated using Lowry's method., Results: There was a significant increase in enzyme activity in the periodontitis groups compared to the non-periodontitis groups ( P <0.001). However, significantly lower enzyme activity was observed among smokers, irrespective of periodontal status ( P <0.001). Nevertheless, a receiver operating characteristic curve analysis indicated the diagnostic potential of both enzymes to be fair-to-excellent., Conclusion: Although smoking was found to significantly alter enzyme activity, LDH and β-glucuronidase were reliable salivary biomarkers of periodontitis among both smokers and non-smokers., Competing Interests: CONFLICT OF INTEREST The authors declare no conflicts of interest.

Objective: The purpose of this study was to compare the effects of the oral administration of natural curcumin and a chemically modified curcumin (CMC2.24) on osteoclast-mediated bone resorption, apoptosis, and inflammation in a murine model of experimental periodontal disease., Design: Fifty male rats were distributed among the following treatment groups: (i) 2% carboxymethylcellulose, (ii) CMC2.24 30 mg/kg body weight, (iii) Curcumin 100 mg/kg body weight and (iv) no treatment. Compounds were administered daily by oral intubation over a 15-day period of time. Periodontal disease was induced by injections of LPS (lipopolysaccharide) into the gingival tissues three times per week. Contralateral sides were injected with the same volume of PBS (phosphate buffered saline) vehicle. After 15 days, hemimaxillae and gingival tissues were harvested. Bone resorption was assessed by μCT (microcomputer tomography). Formalin-fixed, paraffin embedded histological sections were stained with haematoxylin/eosin (H/E) for the assessment of cellular infiltrate or subjected to immunohistochemistry for detecting TRAP (tartrate-resistant acid phosphatase)-positive cells and caspase-3. Apoptosis was assessed in the gingival tissues by DNA fragmentation., Results: CMC2.24 and curcumin caused a significant reduction of the inflammatory cell infiltrate, however μCT analysis showed that only CMC2.24 reduced bone resorption and the number of TRAP-positive multinucleated cells (osteoclasts). Curcumin, but not CMC2.24, significantly reduced the number of apoptotic cells in the gingival tissues and of osteocytes in the alveolar bone crest., Conclusions: The results suggest that CMC2.24 and curcumin inhibit inflammation by different mechanisms, but only CMC2.24 was capable of reducing alveolar bone resorption in the LPS-induced model of periodontitis., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Periodontal disease is the most common cause of tooth loss in humans, is an inflammatory disease initiated by oral microbial biofilm. Given the involvement of the inflammatory pathway in this type of pathology, the main pharmacological strategy for the treatment of periodontitis, is the inhibition of the inflammatory process in order to prevent tissue destruction and bone resorption, a condition associated with a painful state. To do this, the best class of drugs are Non-steroidal anti-inflammatory drugs (NSAIDs), however, the presence of side effects, especially at the gastrointestinal tract, limits their use for long-term therapy. Recently, some evidence shows that derivatives of NSAIDs capable of releasing hydrogen sulphide exhibit lower collateral effects, particularly at the gastric level. In fact, H2S is an endogenous gaseous mediator with a cytoprotective role at the gastric level. In this study, we have compared the protective effects of ketoprofen with ATB-352, a hydrogen sulfide-releasing derivative of ketoprofen, in an experimental model of periodontitis in rat. Periodontitis was induced by a single intragingival injection of 1 μl LPS (10 μg/μl), Our results show that 14 h after intragingival injection of LPS, there was a high tissue damage associated with bone resorption, and in gingivomucosal tissues there was a significant expression of NF-kb p65 and pro-inflammatory cytokine as well as a higher expression of COX-2 and iNOS, activation of the apoptotic process, and also increased levels of NGF expression, often associated with a higher nociceptive perception. Treatment with ATB-352 at the dose of 20mg\kg, was able to reduce the inflammatory process associated with intragingival LPS injection and also had a positive effect on bone resorption and tissue damage., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Nicotine is associated with increased incidence of periodontal disease and poor response to therapy. This article aimed at identifying the expression of matrix metalloproteinases 2 (MMPs2) and vascular endothelial growth factor (VEGF) proteins on extracellular matrix, fibrous distribution and angiogenetic development in periodontitis caused by nicotine effects on periodontal membrane., Materials and Methods: In this experimental study, rats were divided into nicotine and control groups. While the rats in the nicotine group (n = 6) were administered 2 mg/kg nicotine sulphate for 28 days, the animals in the control group (n = 6) were only administered 1.5 mL physiologic saline solution subcutaneously for 28 days., Results: Histological sections were prepared and immunohistochemically stained for MMP2 and VEGF. The sections stained with Trichrome-Masson were observed under light microscope. VEGF and MMP2 immunoreactivity of periodontal gingiva and dentin was assessed by immunohistochemical staining., Conclusions: Nicotine reduces MMP production, disrupts collagen synthesis and causes periodontitis. We observed that nicotine increases periodontitis by disrupting periodontal membrane and prevents tooth to anchor in dental alveoli by disrupting epithelial structure.

Purpose: The aim of this study was to evaluate the effects of low-level laser therapy (LLLT) and antimicrobial photodynamic therapy (aPDT) as adjuvant to mechanical treatment of experimental periodontitis (EP) in adult rats submitted to 5-fluorouracil (5-FU) chemotherapy., Methods: EP was induced through ligature around the left mandibular first molar for 7 days. The ligature was removed and the animals separated into groups: EP, no treatment; 5FU, systemic administration of 5-FU (80 and 40 mg/kg); 5FU/scaling and root planing (SRP), systemic application of 5-FU and SRP; 5FU/SRP/LLLT, systemic application of 5-FU, SRP, and LLLT (660 nm, 0.035 W; 29.4 J/cm 2 ); and 5FU/SRP/aPDT, systemic application of 5-FU, SRP, and aPDT (methylene blue irrigation and LLLT). The animals were euthanized 7, 15, and 30 days after treatments. Histological sections from mandibles were processed for histomorphometric and immunohistochemical analysis (TRAP, RANKL, OPG, TNF-α, IL-6, IL-10). The alveolar bone loss (BL) area in the furcation region of the mandibular first molar was analyzed histometrically., Results: There was less bone loss in 5FU/SRP/aPDT compared with 5FU at 7 days (p < 0.05). The immunohistochemical analysis showed no significant difference for TRAP and osteoprotegerin, but lower RANKL immunolabeling was observed in the 5FU/SRP/LLLT and 5FU/SRP/aPDT groups compared with the 5FU group at 15 days. There was lower TNF-α and IL-6 immunolabeling in the 5FU/SRP/LLLT and 5FU/SRP/aPDT groups and higher IL-10 immunolabeling in 5FU/SRP/aPDT at 30 days., Conclusion: LLLT and aPDT adjuvant to SRP minimized the effects of 5-FU on periodontal disease. Furthermore, aPDT promoted greater benefits in bone loss control and inflammatory response.

Chronic inflammatory diseases, such as periodontal disease, associate with adverse wound healing in response to myocardial infarction (MI). The goal of this study was to elucidate the molecular basis for impaired cardiac wound healing in the setting of periodontal-induced chronic inflammation. Causal network analysis of 168 inflammatory and extracellular matrix genes revealed that chronic inflammation induced by a subseptic dose of Porphyromonas gingivalis lipopolysaccharide (LPS) exacerbated infarct expression of the proinflammatory cytokine Ccl12. Ccl12 prevented initiation of the reparative response by prolonging inflammation and inhibiting fibroblast conversion to myofibroblasts, resulting in diminished scar formation. Macrophage secretion of Ccl12 directly impaired fibronectin and collagen deposition and indirectly stimulated collagen degradation through upregulation of matrix metalloproteinase-2. In post-MI patients, circulating LPS levels strongly associated with the Ccl12 homologue monocyte chemotactic protein 1 (MCP-1). Patients with LPS levels ≥ 1 endotoxin units (EU)/ml (subseptic endotoxemia) at the time of hospitalization had increased end diastolic and systolic dimensions compared with post-MI patients with < 1 EU/ml, indicating that low yet pathological concentrations of circulating LPS adversely impact post-MI left ventricle (LV) remodeling by increasing MCP-1. Our study provides the first evidence to our knowledge that chronic inflammation inhibits reparative fibroblast activation and generates an unfavorable cardiac-healing environment through Ccl12-dependent mechanisms.

The purpose of this study was to assess the effect of a novel chemically modified curcumin (CMC 2.24) on NF-κB and MAPK signaling and inflammatory cytokine production in two experimental models of periodontal disease in rats. Experimental model I: Periodontitis was induced by repeated injections of LPS into the gingiva (3×/week, 3 weeks); control rats received vehicle injections. CMC 2.24, or the vehicle, was administered by daily oral gavage for 4 weeks. Experimental model II: Diabetes was induced in adult male rats by streptozotocin injection; periodontal breakdown then results as a complication of uncontrolled hyperglycemia. Non-diabetic rats served as controls. CMC 2.24, or the vehicle, was administered by oral gavage daily for 3 weeks to the diabetics. Hemimaxillae and gingival tissues were harvested, and bone loss was assessed radiographically. Gingival tissues were pooled according to the experimental conditions and processed for the analysis of matrix metalloproteinases (MMPs) and bone-resorptive cytokines. Activation of p38 MAPK and NF-κB signaling pathways was assessed by western blot. Both LPS and diabetes induced an inflammatory process in the gingival tissues associated with excessive alveolar bone resorption and increased activation of p65 (NF-κB) and p38 MAPK. In both models, the administration of CMC 2.24 produced a marked reduction of inflammatory cytokines and MMPs in the gingival tissues, decreased bone loss, and decreased activation of p65 (NF-κB) and p38 MAPK. Inhibition of these cell signaling pathways by this novel tri-ketonic curcuminoid (natural curcumin is di-ketonic) may play a role in its therapeutic efficacy in locally and systemically associated periodontitis.

Bone-loss-related diseases such as rheumatoid arthritis, osteomyelitis, osteoporosis, and periodontitis are associated with high rates of morbidity worldwide. These disorders are characterized by an imbalance between the formation and activity of osteoblasts and osteoclasts, leading to bone loss. In this context, we evaluated the effect of cinnamoyloxy-mammeisin (CNM), an anti-inflammatory coumarin found in Melipona scutellaris geopropolis, on key targets related to bone remodeling. In the present study we investigated the in vitro effects of CNM on osteoclast differentiation and M-CSF+RANKL-induced osteoclastogenic marker expression. Additionally, the interference of CNM treatment on osteoclast activity was evaluated by zymography and resorption area. Finally, we assessed the capacity of the compound to mitigate alveolar bone loss in vivo in experimental murine periodontitis induced by Porphyromonas gingivalis. We observed that treatment with CNM impaired osteoclast differentiation, as evidenced by a reduced number of tartrate-resistant acid-phosphatase-positive multinucleated cells (TRAP+) as well as the expression of osteoclastogenic markers upon M-CSF+RANKL-induced stimulation. Similarly, we observed reduced gelatinolytic and resorption capacity in M-CSF+RANKL-induced cells in vitro. Lastly, CNM attenuated alveolar bone loss in an experimental murine periodontitis model. These findings indicate that CNM may be considered a promising treatment for bone loss diseases.

Background: Periodontal inflammation causes endothelial dysfunction of the systemic artery. However, it is unknown whether the use of local anesthetics during painful dental procedures alleviates periodontal inflammation and systemic endothelial function. This study was designed to examine whether the gingival or systemic injection of lidocaine prevents oxidative stress-induced endothelial dysfunction of the systemic artery in rats with intermittent periodontal inflammation caused by lipopolysaccharides (LPS)., Methods: Some rats received 1500 µg LPS injections to the gingiva during a week interval from the age of 8 to 11 weeks (LPS group). Lidocaine (3 mg/kg), LPS + lidocaine (3 mg/kg), LPS + lidocaine (1.5 mg/kg), and LPS + lidocaine (3 mg/kg, IP) groups simultaneously received gingival 1.5 or 3 mg/kg or IP 3 mg/kg injection of lidocaine on the same schedule as the gingival LPS. Isolated aortas or mandibles were subjected to the evaluation of histopathologic change, isometric force recording, reactive oxygen species, and Western immunoblotting., Results: Mean blood pressure and heart rate did not differ among the control, LPS, LPS + lidocaine (3 mg/kg), and lidocaine (3 mg/kg) groups. LPS application reduced acetylcholine (ACh, 10 to 10 mol/L)-induced relaxation (29% difference at ACh 3 × 10 mol/L, P = .01), which was restored by catalase. Gingival lidocaine (1.5 and 3 mg/kg) dose dependently prevented the endothelial dysfunction caused by LPS application (24.5%-31.1% difference at ACh 3 × 10 mol/L, P = .006 or .001, respectively). Similar to the gingival application, the IP injection of lidocaine (3 mg/kg) restored the ACh-induced dilation of isolated aortas from rats with the LPS application (27.5% difference at ACh 3 × 10 mol/L, P < .001). Levels of reactive oxygen species were double in aortas from the LPS group (P < .001), whereas the increment was abolished by polyethylene glycol-catalase, gingival lidocaine (3 mg/kg), or the combination. The LPS induced a 4-fold increase in the protein expression of tumor necrosis factor-α in the periodontal tissue (P < .001), whereas the lidocaine (3 mg/kg) coadministration partly reduced the levels. Lidocaine application also decreased the protein expression of the nicotinamide adenine dinucleotide phosphate oxidase subunit p47phox, which was enhanced by the gingival LPS (5.6-fold increase; P < .001)., Conclusions: Lidocaine preserved the aortic endothelial function through a decrease in arterial reactive oxygen species produced by nicotinamide adenine dinucleotide phosphate oxidase and periodontal tumor necrosis factor-α levels in rats with periodontal inflammation. These results suggest the beneficial effect of the gingival application of local anesthetics on the treatment of periodontal diseases on endothelial function of systemic arteries.

Ethnopharmacological Relevance: Salvia sclarea L., clary, is an aromatic plant traditionally used in folk medicine for the treatment of various diseases and conditions. Although it has been primarily used as a stomachic, there are data on traditional use of S. sclarea as an agent against gingivitis, stomatitis and aphthae., Aim of the Study: The aim of the study was to examine the effect of the S. sclarea ethanolic extract on the lipopolysaccharide (LPS)-induced periodontitis in rats from the immunological and histopathological standpoint., Material and Methods: Periodontal inflammation in rats was induced by repeated injections of LPS from Escherichia coli into the interdental papilla between the first and second right maxillary molars. The extract was administered two times a day by oral gavage (200mg/kg body weight). The inflammatory status was assessed by the measurements of proinflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) of gingival tissues and descriptive analysis of histological sections of periodontium. Chemical characterization of the extract was determined using high performance liquid chromatography system (HPLC). Antioxidant activity of the extract was estimated with two in vitro complementary methods: 2,2-diphenyl-1-picrylhydrazyl and β-carotene/linoleic acid models., Results: Treatment with S. sclarea extract, compared to the untreated group of the rats, significantly diminished the process of inflammation decreasing the levels of IL-1β, IL-6 and TNF-α, reducing the gingival tissue lesions and preserving bone alveolar resorption. Considerably smaller number of inflammatory cells and larger number of fibroblasts was noticed. The administration of the extract three days earlier did not have significant preventive effects. Rosmarinic acid was the predominant compound in the extract. The extract showed strong antioxidant effects in both test systems., Conclusions: S. sclarea extract manifested anti-inflammatory effect in LPS-induced periodontitis suggesting that it may have a role as a therapeutic agent in periodontal diseases. Having in mind that overproduction of reactive oxygen species is connected to periodontitis, the strong antioxidant capacity may be contributable to anti-inflammatory properties of the extract., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Data sourcesMedline (PubMed), Embase, Cochrane Central Register of Controlled Trials and Cochrane Oral Health Group Trials Register databases and a manual search of the Journal of Dental Research, Journal of Clinical Periodontology, Journal of Periodontology and the International Journal of Periodontics and Restorative Dentistry from January 2014 to February 2015.Study selectionProspective, retrospective, randomised or not, case-controlled or case series trials showing the incidence or recurrence of peri-implant disease plus or minus PIMT over more than six months.Data extraction and synthesisThree reviewers independently selected studies and abstracted data with two reviewers assessing study quality using the Newcastle-Ottawa Scale (NOS). A multivariate binomial regression was used to examine the data.ResultsThirteen studies were included with ten contributing to the meta-analysis. The average quality assessment score (NOS) was 5.3 out of a possible nine, only one paper achieved eight. At patient level mucositis ranged from 18.5-74.2% and peri-implantitis from 8-28%, with significant effects being seen for treatment (z= -14.36, p<0.001). Mucositis was affected by history of periodontitis and mean PIMT at implant and patient levels, respectively. For peri-implantitis there were also significant effects of treatment (z = -16.63, p<0.001). Increased peri-implantitis was observed for patients with a history of periodontal disease. (z=3.76, p<0.001). Implants under PIMT have 0.958 the incident event compared to those with no PIMT.ConclusionsWithin the limitations of the present systematic review it can be concluded that implant therapy must not be limited to placement and restoration of dental implants, but to the implementation of PIMT to potentially prevent biological complications and heighten the long-term success rate. Although it must be tailored to a patients risk profiling, our findings suggest reason to claim a minimum recall PIMT interval of five to six months. Additionally, it must be stressed that even in the establishment of PIMT, biological complications might occur. Hence, patient-, clinical-, and implant-related factors must be thoroughly explored.

Background: We reported that high-fat diet (HFD)-induced metabolic syndrome (MetS) exacerbates lipopolysaccharide (LPS)-stimulated periodontitis and palmitate, the major saturated fatty acid in the HFD, amplified LPS-stimulated gene expression in vitro. As CD36 is a major receptor for fatty acids, we investigated periodontal CD36 expression in mice with periodontitis and MetS, and the role of CD36 in inflammatory gene expression in macrophages stimulated by palmitate., Methods: MetS and periodontitis were induced in mice by HFD and periodontal injection of LPS, respectively. The periodontal CD36 expression and its relationship with alveolar bone loss were studied using immunohistochemistry, real-time PCR, and correlation analysis. The role of CD36 in upregulation of inflammatory mediators by LPS and palmitate in macrophages was assessed using pharmacological inhibitor and small interfering RNA., Results: Periodontal CD36 expression was higher in mice with both MetS and periodontitis than that in mice with periodontitis or MetS alone and was correlated with osteoclastogenesis and alveolar bone loss. In vitro studies showed that CD36 expression in macrophages was upregulated by LPS and palmitate, and targeting CD36 attenuated palmitate-enhanced gene expression., Conclusion: CD36 expression is upregulated in mice with periodontitis and MetS and involved in gene expression in macrophages stimulated by palmitate and LPS., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Overview: There is a lack of clinical research on the potential effect of cannabis use on the periodontium as well as its effect on treatment outcomes. The aim of this case report is to illustrate the clinical presentation of periodontal disease in a young woman who was a chronic cannabis user, as well as successful treatment involving motivating the patient to quit cannabis use and undergo nonsurgical and surgical therapy., Case Description: A 23-year-old woman sought care at the dental clinic for periodontal treatment. During a review of her medical history, the patient reported using cannabis frequently during a 3-year period, which coincided with the occurrence of gingival inflammation. She used cannabis in the form of cigarettes that were placed at the mandibular anterior region of her mouth for prolonged periods. Localized prominent papillary and marginal gingival enlargement of the anterior mandible were present. The mandibular anterior teeth showed localized severe chronic periodontitis. The clinicians informed the patient about the potentially detrimental consequences of continued cannabis use; she was encouraged to quit, which she did. The clinicians performed nonsurgical therapy (scaling and root planing) and osseous surgery. The treatment outcome was evaluated over 6 months; improved radiographic and clinical results were observed throughout the follow-up period., Conclusions and Practical Implications: Substantial availability and usage of cannabis, specifically among young adults, requires dentists to be vigilant about clinical indications of cannabis use and to provide appropriate treatments. Behavioral modification, nonsurgical therapy, and surgical therapy offer the potential for successful management of cannabis-related periodontitis., (Copyright © 2017 American Dental Association. Published by Elsevier Inc. All rights reserved.)