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The morphology of the alveolar bone at the maxillary anterior teeth in periodontitis patients was evaluated by cone-beam computed tomography (CBCT) to investigate the distribution of alveolar defects and provide guidance for clinical practice. Ninety periodontitis patients and 30 periodontally healthy individuals were selected to determine the morphology of the alveolar bone at the maxillary anterior teeth according to the degree of bone loss, tooth type, sex and age. The differences in the dimensions between periodontitis patients and healthy individuals were compared, and the distribution of alveolar bone defects was analyzed. A classification system was established regarding the sagittal positions and angulations of the teeth. The buccal residual bone was thicker and the lingual bone was thinner in the periodontitis patients than in the periodontally healthy individuals, and there were differences between the different tooth types, sexes and age subgroups. The buccal undercut was close to the alveolar ridge, while fenestration was reduced and the apical bone height was higher in periodontitis patients than in periodontally healthy individuals. The apical bone height increased with the aggravation of bone loss and age. The proportions of different sagittal positions changed with the aggravation of bone loss. Moreover, the teeth moved more buccally regarding the positions of the maxillary anterior teeth. The morphology of the alveolar bone at the maxillary anterior teeth differed between periodontitis patients and healthy individuals, and the differences were related to the degree of bone loss, tooth type, sex and age.

Cardiovascular disease is a common cause of morbidity and premature mortality. Cardiovascular disease can be prevented when risk factors are identified early. Calcified carotid artery atheromas (CCAAs), detected in panoramic radiographs, and periodontitis have both been associated with increased risk of cardiovascular disease. This case-control study aimed to 1) investigate associations between periodontitis and CCAA detected in panoramic radiographs and 2) determine the risk of future myocardial infarctions due to CCAA combined with periodontitis. We evaluated 1,482 participants (738 cases and 744 controls) with periodontitis and CCAAs recruited from the PAROKRANK study (Periodontitis and Its Relation to Coronary Artery Disease). Participants were examined with panoramic radiographs, including the carotid regions. Associations between myocardial infarction and periodontitis combined with CCAA were evaluated in 696 cases and 696 age-, sex-, and residential area-matched controls. Periodontitis was evaluated radiographically (as degree of bone loss) and with a clinical periodontal disease index score (from clinical and radiographic assessments). We found associations between CCAA and clinical periodontal disease index score among cases (odds ratio [OR], 1.51; 95% CI, 1.09 to 2.10; P = 0.02) and controls (OR, 1.70; 95% CI, 1.22 to 2.38; P < 0.01), although not between CCAA and the degree of bone loss. In a multivariable model, myocardial infarction was associated with CCAA combined with periodontitis, as assessed by degree of bone loss (OR, 1.75; 95% CI, 1.11 to 2.74; P = 0.01). When the cohort was stratified by sex, only men showed a significant association between myocardial infarction and CCAA combined with periodontitis. Participants with clinically diagnosed periodontitis exhibited CCAA in panoramic radiographs more often than those without periodontitis, irrespective of the presence of a recent myocardial infarction. Participants with combined periodontitis and CCAA had a higher risk of having had myocardial infarction as compared with participants with either condition alone. These findings implied that patients in dental care might benefit from dentists assessing panoramic radiographs for CCAA-particularly, patients with periodontitis who have not received any preventive measures for cardiovascular disease.

Objectives: Visfatin is an adipokine that plays an important role in immune functions as a growth factor, enzyme, and pro-inflammatory mediator. We aimed to determine the levels of visfatin, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in gingival crevicular fluid (GCF) in both obese/non-obese patients, with/without generalized chronic periodontitis (GCP)., Methodology: Patients were categorized as obese (O) (n=31) or non-obese (nO) (n=19). Groups were divided into four subgroups according to periodontal conditions: (1) periodontally healthy without obesity (nO-Ctrl); (2) GCP without obesity (nO-CP); (3) periodontally healthy with obesity (O-Ctrl); and (4) GCP with obesity (O-CP). Demographic variables, anthropometric and laboratory data were recorded. Periodontal parameters were measured at baseline and 3rd months after either non-surgical periodontal treatment or calorie -restricted diet therapy. At the same time, GCF samples were taken from patients to analyze TNF-alpha, IL-6,and visfatin levels., Results: Periodontal parameters were significantly higher in the O group than in the nO group (P<0.05). IL-6 levels were higher in the O group than in the nO group (P<0.001). The visfatin levels of the obese patients were reduceddecreased following the treatments (P<0.05). Cholesterol levels were higher in the O group than in the nO groups (P<0.05). IL-6 levels were higher in O-CP and O-Ctrl groups than in the nO-Ctrl group (P<0.05). Compared to the other groups, visfatin levels were significantly higher in the O-CP group but decreased following treatment (P<0.05)., Conclusions: Our findings suggest that visfatin and IL-6 levels in GCF are associated with the pathogenesis of obesity and periodontitis. Within the limits of this study, we considered that there might be an association between the lipid profile and periodontitis on systemically healthy individuals.

Backgrounds and Objectives: IMD-0354 is a novel I kappa-B kinase (IKK) inhibitor, which regulates inflammation. The purpose of this study was to examine the effect of the reagent on bone loss for ligature-induced periodontitis., Material and Methods: We ligated around the upper right second molars of 8-week-old C57BL/6J mice in the split-mouth model. The test mice were injected intraperitoneally with IMD-0354 before the placement of the ligature. The control mice were injected intraperitoneally with 0.5% carboxymethylcellulose (CMC) as vehicle before the placement of the ligature. To determine the optimum concentration of the reagent on ligature-induced periodontitis in the mice, we examined the effect of three types of concentration, which were 1, 5, and 10 mg/kg of IMD-0354, as a preliminary experiment. After we determined 10 mg/kg as the optimum concentration for the IMD group by micro-CT analysis, both the IMD and CMC groups (n = 15 each in total, including all the analyses) were subdivided into two small groups, respectively, for further analyses: I group (unligated side of IMD group), IL group (ligated side of IMD group), C group (unligated side of CMC group) and CL group (ligated side of CMC group). The mice in the IMD and CMC groups were treated with each reagent daily and sacrificed 8 days after the ligation. For assessment of bone resorption, we performed micro-CT and histological analyses. We also carried out real-time PCR to investigate proinflammatory and bone metabolic markers., Results: There were significant differences for linear bone loss and volumetric parameter in the test (IMD) group compared to the control (CMC) group 8 days after ligation. In terms of the mRNA expression level of gingival tissue, the level of RANKL was significantly suppressed in the IMD group compared to the CMC group. IMD-0354 also tended to suppress the levels of interleukin-1 beta, tumor necrosis factor-alpha, and osteoprotegerin. For histological analysis, the relative numbers of TRAP-positive multinucleated cells decreased significantly in the IMD group compared to the CMC group., Conclusion: IMD-0354 regulated bone resorption by ligature-induced periodontitis, and it is suggested that the inhibition of IKK via down-regulation of NF kappa-B may provide periodontal patients with an effective approach to prevent or suppress the disease., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background:  As dental imaging accounts for approximately 40 % of all X-ray examinations in Germany, profound knowledge of this topic is essential not only for the dentist but also for the clinical radiologist. This review focuses on basic imaging findings regarding the teeth. Therefore, tooth structure, currently available imaging techniques and common findings in conserving dentistry including endodontology, periodontology, implantology and dental trauma are presented., Methods:  Literature research on the current state of dental radiology was performed using Pubmed., Results and Conclusion:  Currently, the most frequent imaging techniques are the orthopantomogram (OPG) and single-tooth radiograph, as well as computer tomography (CT) and cone beam CT mainly for implantology (planning or postoperative control) or trauma indications. Especially early diagnosis and correct classification of a dental trauma, such as dental pulp involvement, prevents from treatment delays or worsening of therapy options and prognosis. Furthermore, teeth are commonly a hidden focus of infection.Since radiologists are frequently confronted with dental imaging, either concerning a particular question such as a trauma patient or regarding incidental findings throughout head and neck imaging, further training in this field is more than worthwhile to facilitate an early and sufficient dental treatment., Key Points:   · This review focuses on dental imaging techniques and the most important pathologies.. · Dental pathologies may not only be locally but also systemically relevant.. · Reporting of dental findings is important for best patient care.., Citation Format: · Masthoff M, Gerwing M, Masthoff M et al. Dental Imaging - A basic guide for the radiologist. Fortschr Röntgenstr 2019; 191: 192 - 198., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

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.)

Objective: We aimed to evaluate molecular imaging as a novel diagnostic tool for mice periodontitis model induced by ligature and Porphyromonas gingivalis (Pg) inoculation., Materials and Methods: Twelve female mice were assigned to the following groups: no treatment as control group (n = 4); periodontitis group induced by ligature and Pg as Pg group (n = 4); and Pg group treated with glycyrrhizinic acid (GA) as Pg + GA group (n = 4). All mice were administered a myeloperoxidase (MPO) activity-specific luminescent probe and observed using a charge-coupled device camera on day 14. Image analysis on all mice was conducted using software to determine the signal intensity of inflammation. Additionally, histological and radiographic evaluation for periodontal inflammation and bone resorption at the site of periodontitis, and quantitative enzyme-linked immunosorbent assay (ELISA) were conducted on three mice for each group. Each experiment was performed three times., Results: Levels of serum IgG antibody against P. gingivalis were significantly higher in the Pg than in the Pg + GA group. Histological analyses indicated that the number of osteoclasts and neutrophils were significantly lower in the Pg + GA than in the Pg group. Micro-CT image analysis indicated no difference in bone resorption between the Pg and Pg + GA groups. The signal intensity of MPO activity was detected on the complete craniofacial image; moreover, strong signal intensity was localized specifically at the periodontitis site in the ex vivo palate, with group-wise differences., Conclusions: Molecular imaging analysis based on MPO activity showed high sensitivity of detection of periodontal inflammation in mice., Clinical Relevance: Molecular imaging analysis based on MPO activity has potential as a diagnostic tool for periodontitis.

Deepened periodontal pockets exert a significant pathological burden on the host and its immune system, particularly in a patient with generalized moderate to severe periodontitis. This burden is extensive and longitudinal, occurring over decades of disease development. Considerable diagnostic and prognostic successes in this regard have come from efforts to measure the depths of the pockets and their contents, including level of inflammatory mediators, cellular exudates and microbes; however, the current standard of care for measuring these pockets, periodontal probing, is an analog technology in a digital age. Measurements obtained by probing are variable, operator dependent and influenced by site-specific factors. Despite these limitations, manual probing is still the standard of care for periodontal diagnostics globally. However, it is becoming increasingly clear that this technology needs to be updated to be compatible with the digital technologies currently being used to image other orofacial structures, such as maxillary sinuses, alveolar bone, nerve foramina and endodontic canals in 3 dimensions. This review aims to summarize the existing technology, as well as new imaging strategies that could be utilized for accurate evaluation of periodontal pocket dimensions., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Food-derived peptides have been reported to exhibit antibacterial activity against periodontal pathogenic bacteria. However, no effect has been shown on inflammation and bone resorption in periodontal pathology. The overall objective of the current study was to investigate how rice peptides influence biological defense mechanisms against periodontitis-induced inflammatory bone loss, and identify their novel functions as a potential anti-inflammatory drug., Design: The expression of inflammatory and osteoclast-related molecules was examined in mouse macrophage-derived RAW 264.7 cell cultures using qPCR. Subsequently, the effect of these peptides on inflammatory bone loss in mouse periodontitis was examined using a mouse model of tooth ligation. Briefly, periodontal bone loss was induced for 7 days in mice by ligating the maxillary second molar and leaving the contralateral tooth un-ligated (baseline control). The mice were microinjected daily with the peptide in the gingiva until the day before euthanization. One week after the ligation, TRAP-positive multinucleated cells (MNCs) were enumerated from five random coronal sections of the ligated sites in each mouse., Results: Rice peptides REP9 and REP11 significantly inhibited transcription activity of inflammatory and osteoclast-related molecules. Local treatment with the rice peptides, in mice subjected to ligature-induced periodontitis, inhibited inflammatory bone loss, explaining the decreased numbers of osteoclasts in bone tissue sections., Conclusion: Therefore, these data suggested that the rice peptides possess a protective effect against periodontitis., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to investigate the titanium (Ti) content of biopsies from patients with severe peri-implantitis or controls without Ti exposure., Background: Peri-implantitis is considered to be an infectious disease, but recent studies have shown that Ti can aggravate inflammation in combination with bacterial products. The Ti content of peri-implantitis and periodontitis (controls) tissue is unknown., Methods: Thirteen patients referred for peri-implantitis and eleven for periodontitis treatment were included in the study. Disease severity was obtained from dental records. Biopsies were taken from both groups and chemically analysed with inductively coupled plasma mass spectrometry for Ti content. Additionally, two patients with peri-implantitis and two with periodontitis were recruited and their biopsies were analysed microscopically with light microscopy, transmission electron microscopy and scanning electron microscopy with element analysis to investigate the presence of particulate Ti., Results: All patients lost one or more implants despite undergoing peri-implant or treatment. Peri-implantitis tissue contained significantly higher concentrations of Ti than control samples with a mean ± SD of 98.7 ± 85.6 and 1.2 ± 0.9 μg/g, respectively. Particulate metal was identified in peri-implantitis and control biopsies, but element analyses could confirm only the presence of Ti in peri-implantitis tissue., Conclusion: We showed that high contents of particulate and submicron Ti were present in peri-implantitis tissue. These high Ti contents in peri-implant mucosa can potentially aggravate inflammation, which might reduce the prognosis of treatment interventions., (© 2018 John Wiley & Sons Ltd.)

The aim of this split-mouth clinical and radiographic study was to evaluate and compare the regenerative potential of a combination of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and beta tricalcium phosphate (β-TCP) to the established technique of bone grafting with β-TCP alone in the surgical management of intraosseous defects. A total of 24 sites in 12 subjects with intraosseous defects were included and randomly divided into test (rhPDGF-BB + β-TCP) and control (β-TCP alone) sites. Clinical parameters were recorded at baseline, 3 months, and 6 months. Radiographic parameters were evaluated at baseline and 6 months. Both groups showed statistically significant reductions of all clinical parameters. Intergroup comparison demonstrated a significantly greater probing pocket depth reduction and clinical attachment level gain in the test group. The mean percentage defect fill was significantly greater in the test group than in the control group at 3 and 6 months, and greater improvement in defect angle was also evident in the test group. Although both groups showed definitive improvements in all parameters, the test group showed significantly better results when used to treat human periodontal intraosseous defects.

Spacing between the maxillary anterior teeth is a common concern for young patients and their parents. Patients often consider a diastema to be an annoying but minor problem; they might consult their general dentists for help, or try to address the issue themselves by applying elastic "gap bands." Moreover, parents, without any informed consent, sometimes accept this erroneous method as an easy and inexpensive treatment approach. A 9-year-old boy had severe acute periodontitis involving the maxillary central incisors caused by the placement of an elastic band and its apical migration. Despite periodontal and surgical interventions, the maxillary central incisors were finally extracted, and the patient started orthodontic treatment. The orthodontic treatment plan included maxillary lateral incisor substitution to replace the lost central incisors and mesialization of the maxillary posterior dentition. An interdisciplinary approach with excellent cooperation among the orthodontist, general dentist, and other dental specialists obtained an esthetically pleasing and optimized functional result. Treating the diastema between the anterior teeth with elastic gap bands and without fixed orthodontic appliances should be avoided. Patients should seek proper orthodontic advice for even small-scale orthodontic problems to prevent catastrophic outcomes, as exhibited in this case report., (Copyright © 2018 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

This study aimed to verify, in in vivo settings, whether quorum-sensing inhibition molecules could attenuate alveolar bone loss induced by Porphyromonas gingivalis/Fusobacterium nucleatum co-infection and reduce the bacterial colonization of periodontal tissues. In BALB/c mice, periodontitis was induced through oral inoculation with P. gingivalis and F. nucleatum six times during a 42-d period. Quorum sensing inhibitors (a furanone compound and D-ribose) were administered simultaneously with bacterial infection. Linear and volumetric modifications of interproximal alveolar bone levels were compared between groups using micro-computed tomography. Total bacteria, and P. gingivalis and F. nucleatum DNA in periodontal tissues, were quantified using real-time PCR. Radiographic linear measurements demonstrated a significant reduction of alveolar bone loss, of approximately 40%, in mice treated with quorum sensing inhibitors when compared with the co-infection group. This was confirmed by a significant increase of residual bone volume in the test group. While total bacterial genes in the treatment group significantly decreased by 93% in periodontal tissue samples when quorum sensing inhibitors were administered, no significant differences of P. gingivalis DNA were found. Quorum sensing inhibitors reduced periodontal breakdown and bacterial infection in periodontal tissues after co-infection with P. gingivalis and F. nucleatum., (© 2018 Eur J Oral Sci.)

Background and Objective: Elevated levels of matrix metalloproteinase-7 (MMP7) have been observed in serum samples of subjects with type 2 diabetes mellitus (T2DM) and in gingival tissues of subjects with periodontitis. The aim of the present study was to collect in vivo and in silico evidence on the role of MMP7 in the interplay between T2DM and generalized periodontitis (GP)., Material and Methods: The extent of MMP7 expression and localization were immunohistochemically analyzed in gingival tissues of patients with GP with T2DM (T2DM/GP, n = 11), systemically healthy patients with GP (n = 7), and systemically and periodontally healthy controls (n = 11). An in silico network model was built to determine the interactions between MMP7 and T2DM pathways. Regulation of neutrophil transmigration by MMP7 was analyzed in a knock-out mice model., Results: In human gingival tissues, the proportion of cells with robust MMP7 expression was elevated in patients with T2DM/GP in comparison to controls (P = .014). According to the in silico analysis, "hydroxyl radical" and "hydrogen peroxide" compounds were among the most central nodes of the network, and were within the shortest paths connecting "glucose" to "MMP7." In MMP7 knock-out mice, an intense accumulation of neutrophils was observed in the gingival epithelium as compared to wild-type mice (P = .0001)., Conclusion: Elevated MMP7 expression in gingival tissues of patients with T2DM/GP is related to the activation of reactive oxygen species by hyperglycemia. Suppression of MMP7 expression results in impaired neutrophil transmigration in gingiva., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Objective: Melatonin deficiency has been associated with obesity and systemic inflammation. This study aims to evaluate whether melatonin could interfere with the mechanisms of co-morbidity linking obesity and periodontitis., Material and Methods: Twenty-eight male Wistar rats were randomly divided in 4 groups: control group (Con) (fed with standard diet); high-fat diet group (HFD) (fed with a diet containing 35.2% fat); Con group with induced periodontitis (Con-Perio) and HFD group with induced periodontitis (HFD-Perio). To induce periodontitis, the method of oral gavages with Porphyromonas gingivalis ATCC W83K1 and Fusobacterium nucleatum DMSZ 20482 was used. Circulating melatonin levels were analyzed by multiplex immunoassays. Periodontitis was assessed by alveolar bone loss (micro-computed tomography and histology) and by surrogate inflammatory outcomes (periodontal pocket depth, modified gingival index and plaque dental index)., Results: Plasma melatonin levels were significantly decreased (P < .05) in the obese rats with periodontitis when compared with controls or with either obese or periodontitis rats. Alveolar bone loss increased 27.71% (2.28 µm) in HFD-Perio group compared with the Con group. The histological analysis showed marked periodontal tissue destruction with osteoclast activity, particularly in the HFD-Perio group. A significant negative correlation (P < .05) was found between periodontal pocket depth, modified gingival index and circulating melatonin levels., Conclusion: Obese and periodontitis demonstrated significantly lower melatonin concentrations when compared with controls, but in obese rats with periodontitis these concentrations were even significantly lower when compared with either periodontitis or obese rats. These results may indicate that melatonin deficiency could be a key mechanism explaining the co-morbidity effect in the association between obesity and periodontitis., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To investigate the effect of sildenafil citrate on the prevention and progression of experimental periodontitis (EP) in rats., Materials and Methods: Thirty-six male Wistar rats were randomly assigned into two groups: Group 1 (preventive) and Group 2 (progression). In Group 1, the animals received daily doses of sildenafil (10 mg/kg) or vehicle for 30 days, and EP was induced on the 15th day. In Group 2, the EP was induced on the first day, and the animals received daily doses of sildenafil (10 mg/kg) or vehicle from the 15 th day. For EP, ligatures were placed around the right first mandibular molars. Microtomographic, histomorphometric and histological analyses were carried out to evaluate the alveolar bone loss and inflammatory degree. For statistical analyses, t test and the Mann-Whitney test were used, considering a level of significance of 95%., Results: In Group 2, the animals treated with sildenafil showed a significantly lower bone resorption (p = .05). Similarly, the subgroup treated with sildenafil displayed a significantly lesser degree of inflammation (p = .01). No significant differences were observed between the subgroups of the Group 1., Conclusions: Sildenafil decreased the inflammatory process, as well as the alveolar bone loss when used to modulate the progression of experimental periodontitis., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)

Background: Curcumin exhibits anti-inflammatory effects and has been suggested as a treatment for inflammatory diseases. The aim of this study was to investigate the effects of curcumin on the lipopolysaccharide induced inflammatory response in rat gingival fibroblasts in vitro and ligation-induced experimental periodontitis in vivo, and to speculate the possible anti-inflammatory mechanism of curcumin., Methods: The gingival fibroblasts were incubated with different concentrations of curcumin in the absence or presence of lipopolysaccharide (LPS). Concentrations of interleukin-1β(IL-1β), tumor necrosis factor-α (TNF-α), osteoprotegerin (OPG) and soluble receptor activator of nuclear factor kappa-B ligand (RANKL) culture supernatants of rat gingival fibroblasts were determined by enzyme linked immunosorbent assay. The nuclear fraction of rat gingival fibroblasts was extracted and nuclear factor kappa-B (NF-κB) activation was assessed by western blotting to elucidate related mechanisms. Curcumin was given every two days by oral gavage. The gingival inflammation and alveolar bone loss between the first and second molars were observed by hematoxylin and eosin staining. Collagen fibers were observed by picro-sirius red staining. Alveolar bone loss was assessed by micro-CT analysis., Results: Curcumin attenuated the production of IL-1β and TNF-α in rat gingival fibroblasts stimulated by LPS, and inhibited the LPS-induced decrease in OPG/sRANKL ratio and NF-κB activation. Curcumin significantly reduced gingival inflammation and modulated collagen fiber and alveolar bone loss in vivo., Conclusions: curcumin modulates inflammatory activity in rat periodontitis by inhibiting NF-κB activation and decreasing the OPG/sRANKL ratio induced by LPS.

Periodontitis (PD) is characterized by bacterial infection and inflammation of tooth-supporting structures and can lead to tooth loss. PD affects ∼47% of the US population over age 30 years and has a heritability of about 50%. Although the host immunoinflammatory response and genetic background play a role, little is known of the underlying genetic factors. We examined natural genetic variation in lipopolysaccharide (LPS)-induced PD across a panel of inbred mouse strains, the hybrid mouse diversity panel (HMDP). We observed a strain-dependent sixfold difference in LPS-induced bone loss across the HMDP with a heritability of 53%. We performed a genomewide association study (GWAS) using FAST-LMM, which corrects for population structure, and identified loci significantly associated with PD. We examined candidate genes at a locus on chromosome 5, which suggested a relationship between LPS-induced bone loss and, together with expression data, identified Cxcl family members as associated with PD. We observed an increase in Cxcl10 protein, as well as immune cells and pro-inflammatory cytokines in C57BL/6J (high bone loss strain) but not in A/J (low bone loss strain) after LPS injections. Genetic deletion of CXCR3 (Cxcl9 and10 receptor) demonstrated a ∼50% reduction in bone loss and reduced osteoclasts after LPS injections. Furthermore, WT mice treated with AMG-487 (a CXCR3 antagonist) showed a ∼45% reduction in bone loss and decreased osteoclasts after LPS injections. We conclude that CXCR3 is a strong candidate for modulating the host response in individuals susceptible to PD. © 2018 American Society for Bone and Mineral Research., (© 2018 American Society for Bone and Mineral Research.)

Nuclear medicine studies evaluate physiology on a molecular level providing earlier detection of lesions before morphologic change is evident. 99m Tc-MDP and 18 F-fluoride bone scans detect osteomyelitis earlier than radiographs and computed tomography (CT); aid in diagnosis of temporomandibular joint disorder; and evaluate activity of condylar hyperplasia, extent of Paget disease, and viability of bone grafts. 18 F-FDG PET/CT distinguish between soft tissue and bone infections and diagnose osteomyelitis complicated by fracture or surgery. FDG PET is more accurate than CT alone and has a major role in staging, restaging, and assessing response to therapy for head and neck malignancies and in detecting sequelae of therapy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The present study was performed to evaluate the impact of smoking status on 6-month clinical outcomes of a regenerative procedure based on enamel matrix derivative and deproteinized bovine bone mineral in the treatment of intraosseous defects accessed with buccal single flap approach. A total of 22 defects were selected in smoking (n = 11) and nonsmoking (n = 11) patients. Regenerative treatment resulted in similar clinical attachment level (CAL) gain in both smokers and nonsmokers. A trend toward lower 6-month CAL gain and probing depth reduction was observed in patients smoking 11 to 20 cigarettes per day compared to those smoking 1 to 10 cigarettes per day.

Periodontitis is an inflammatory autoimmune disease. Treatment should alleviate inflammation, regulate the immune reaction and promote periodontal tissue regeneration. Icariin is the main active ingredient of Epimedii Folium, and it is a promising compound for the enhancement of mesenchymal stem cell function, promotion of bone formation, inhibition of bone resorption, alleviation of inflammation and regulation of immunity. The study investigated the effect of icariin on periodontal tissue regeneration in a minipig model of periodontitis. The minipig model of periodontitis was established. Icariin was injected locally. The periodontal clinical assessment index, a computed tomography (CT) scan, histopathology and enzyme-linked immune sorbent assay (ELISA) were used to evaluate the effects of icariin. Quantitative analysis results 12 weeks post-injection demonstrated that probing depth, gingival recession, attachment loss and alveolar bone regeneration values were (3.72 ± 1.18) mm vs. (6.56 ± 1.47) mm, (1.67 ± 0.59) mm vs. (2.38 ± 0.61) mm, (5.56 ± 1.29) mm vs. (8.61 ± 1.72) mm, and (25.65 ± 5.13) mm 3 vs. (9.48 ± 1.78) mm 3 in the icariin group and 0.9% NaCl group, respectively. The clinical assessment, CT scan, and histopathology results demonstrated significant enhancement of periodontal tissue regeneration in the icariin group compared to the 0.9% NaCl group. The ELISA results suggested that the concentration of interleukin-1 beta (IL-1β) in the icariin group was downregulated compared to the 0.9% NaCl group, which indicates that local injection of icariin relieved local inflammation in a minipig model of periodontitis. Local injection of icariin promoted periodontal tissue regeneration and exerted anti-inflammatory and immunomodulatory function. These results support the application of icariin for the clinical treatment of periodontitis.

Psoralen and angelicin are two effective compounds isolated from psoraleae, a traditional Chinese medicine. They have a wide range of applications for bone disease treatment and immune modulation. In this study, we explored their new applications for the treatment of periodontal diseases. This study aimed to investigate the effects of psoralen and angelicin on Porphyromonas gingivalis growth and P. gingivalis -derived lipopolysaccharide (Pg-LPS)-induced inflammation, and further to evaluate their effects on osteogenesis. Finally, the effects of angelicin on a mouse model of periodontitis were also investigated. The results showed that psoralen and angelicin had beneficial dose-dependent effects regarding the inhibition of planktonic P. gingivalis and biofilms of P. gingivalis . There were no significant differences in the viability of monocyte-like THP-1 cells and human periodontal ligament cells (hPDLCs) treated with either psoralen or angelicin compared to the untreated control cells. Psoralen and angelicin also markedly decreased the mRNA expression and release of inflammatory cytokines (interleukin [IL]-1β and IL-8) by THP-1 cells in a dose-dependent manner. They significantly enhanced the alkaline phosphatase (ALP) activity of hPDLCs and up-regulated the expression of osteogenic proteins (runt-related transcription factor 2 [RUNX2], distal-less homeobox 5 [DLX5], and osteopontin [OPN]). Angelicin significantly attenuated alveolar bone loss and inflammation response in the mice with periodontitis. In conclusion, our data demonstrated that psoralen and angelicin could inhibit the growth of planktonic P. gingivalis and P. gingivalis biofilm. It is also the first report on the anti-inflammatory effect of psoralen and angelicin against Pg-LPS. They also had an osteogenesis-potentiating effect on hPDLCs. The in vivo study also indicated the effect of angelicin regarding protection against periodontitis. Our study highlighted the potential ability of psoralen and angelicin to act as novel natural agents to prevent and treat periodontitis.

We report a novel method for in situ imaging of microvascular permeability in inflamed gingival tissue, using state-of-the-art Cellvizio™ intravital endoscopic technology and a mouse model of ligature-induced periodontitis. The silk ligature was first placed at the upper left second molar. Seven days later, the ligature was removed, and the animals were intravenously injected with Evans blue. Evans blue dye, which selectively binds to blood albumin, was used to monitor the level of inflammation by monitoring vascular permeability in control non-diseased and ligature-induced experimental periodontitis tissue. More specifically, leakage of Evans blue-bound albumin from the micro-capillary to connective tissue indicates the state of inflammation occurring in the specific site. Evans blue leakage from blood vessels was imaged in situ by directly attaching the endoscope (mini Z tip) of the Cellvizio™ system to the gingival tissue without any surgical incision. Evans blue emission intensity was significantly elevated in gingiva of periodontitis lesions, but not control non-ligature placed gingiva, indicating that this technology can be used as a potential minimally invasive diagnostic tool to monitor the level of inflammation at the periodontal disease site., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Objective: Photodynamic therapy (PDT) and antiresorptive drugs, such as alendronate (ALN), have been shown to reduce alveolar bone loss. The aim of this study was to evaluate the possible synergic effects of combining PDT and ALN on bone loss in periodontitis in rats., Material and Methods: Periodontitis was induced by ligature in 60 Wistar rats randomized into the following groups: control (Group 1); PDT (Group 2); ALN 0.01 mg/kg (Group 3); ALN 0.25 mg/kg (Group 4); PDT + ALN 0.01 mg/kg (Group 5); and PDT + ALN 0.25 mg/kg (Group 6). The rats were killed on day 12 and the mandibles were processed for macroscopic morphometric analysis, micro-computed tomography to analyze bone mineral density (BMD) and histological analysis. Gingival samples were collected to evaluate myeloperoxidase (MPO) and malonaldehyde (MDA) levels., Results: Bone loss and inflammatory activity in histological studies, from the greatest to least was: control > ALN 0.01 mg/kg > PDT > ALN 0.25 mg/kg > PDT + ALN 0.01 mg/kg > PDT + ALN 0.25 mg/kg, while the order from least to greatest BMD was: control < ALN 0.01 mg/kg < PDT < ALN 0.25 mg/kg < PDT + ALN 0.01 mg/kg < PDT + ALN 0.25 mg/kg. The order of MPO and MDA activity from greatest to least was: control > ALN 0.01 mg/kg > PDT > ALN 0.25 mg/kg > PDT + ALN 0.01 mg/kg > PDT + ALN 0.25 mg/kg. The positive results obtained in the group treated with PDT + ALN 0.25 mg/kg showed statistically significant differences (P ≤ .05) compared with the other 5 groups for BMD, MPO and MDA., Conclusion: Combined approach therapy of PDT + ALN 0.25 mg/kg demonstrated a protective effect on alveolar bone loss., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Periodontitis is one of the most common inflammatory human diseases with a strong genetic component. Due to the limited sample size of available periodontitis cohorts and the underlying trait heterogeneity, genome-wide association studies (GWASs) of chronic periodontitis (CP) have largely been unsuccessful in identifying common susceptibility factors. A combination of quantitative trait loci (QTL) mapping in mice with association studies in humans has the potential to discover novel risk loci. To this end, we assessed alveolar bone loss in response to experimental periodontal infection in 25 lines (286 mice) from the Collaborative Cross (CC) mouse population using micro-computed tomography (µCT) analysis. The orthologous human chromosomal regions of the significant QTL were analyzed for association using imputed genotype data (OmniExpress BeadChip arrays) derived from case-control samples of aggressive periodontitis (AgP; 896 cases, 7,104 controls) and chronic periodontitis (CP; 2,746 cases, 1,864 controls) of northwest European and European American descent, respectively. In the mouse genome, QTL mapping revealed 2 significant loci (-log P = 5.3; false discovery rate = 0.06) on chromosomes 1 ( Perio3) and 14 ( Perio4). The mapping resolution ranged from ~1.5 to 3 Mb. Perio3 overlaps with a previously reported QTL associated with residual bone volume in F2 cross and includes the murine gene Ccdc121. Its human orthologue showed previously a nominal significant association with CP in humans. Use of variation data from the genomes of the CC founder strains further refined the QTL and suggested 7 candidate genes ( CAPN8, DUSP23, PCDH17, SNORA17, PCDH9, LECT1, and LECT2). We found no evidence of association of these candidates with the human orthologues. In conclusion, the CC populations enabled mapping of confined QTL that confer susceptibility to alveolar bone loss in mice and larger human phenotype-genotype samples and additional expression data from gingival tissues are likely required to identify true positive signals.

Aim: The effects of green tea on the modulation of vascularization during the progression of spontaneous periodontitis in long-term hyperglycaemia in streptozotocin-induced type 1 diabetic (T1D) rats were evaluated., Materials and Methods: Wistar rats normoglycaemic (NG) and T1D were divided into two control groups, which received water (NG-W and T1D-W) and two experimental groups that received green tea (NG-GT and T1D-GT). Periodontal structures were evaluated by microtomographic and histological analyses. Number of immunostained cells for VEGF (NcVEGF+/mm 2 ) and CD31 (NcCD31+/mm 2 ), as well microvessel density (MVD) in the periodontal ligament (PDL) were evaluated., Results: Long-term hyperglycaemia in T1D-W rats induced vascular alterations in PDL with a reduction of 36% in MVD, a decrease of 33% in NcCD31+/mm 2 and an increase of 53% in NcVEGF+/mm 2 . Concomitantly, a severe degree of periodontitis with higher reduction in bone volume and periodontal bone level was observed. In T1D-GT, green tea maintained the MVD, NcCD31+/mm 2 and NcVEGF+/mm 2 in the PDL similar to normoglycaemic groups. Clinically, in T1D-GT rats, green tea reduced dental plaque accumulation and the degree of periodontitis when compared to T1D-W., Conclusion: Daily green tea consumption has a therapeutic effect on the diabetic vascular disorder in PDL and the progression of periodontitis in long-term hyperglycaemia in T1D rats., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Diabetes mellitus increases periodontitis and pathogenicity of the oral microbiome. To further understand mechanisms through which diabetes affects periodontitis, we examined its impact on periodontal ligament fibroblasts in vivo and in vitro. Periodontitis was induced by inoculation of Porphyromonas gingivalis and Fusobacterium nucleatum in normoglycemic and diabetic mice. Diabetes, induced by multiple low-dose injections of streptozotocin increased osteoclast numbers and recruitment of neutrophils to the periodontal ligament, which could be accounted for by increased CXC motif chemokine 2 (CXCL2) and receptor activator of nuclear factor kappa B ligand (RANKL) expression by these cells. Diabetes also stimulated a significant increase in nuclear factor kappa B (NF-κB) expression and activation in periodontal ligament (PDL) fibroblasts. Surprisingly, we found that PDL fibroblasts express a 2.3-kb regulatory unit of Col1α1 (collagen type 1, alpha 1) promoter typical of osteoblasts. Diabetes-enhanced CXCL2 and RANKL expression in PDL fibroblasts was rescued in transgenic mice with lineage-specific NF-κB inhibition controlled by this regulatory element. In vitro, high glucose increased NF-κB transcriptional activity, NF-κB nuclear localization, and RANKL expression in PDL fibroblasts, which was reduced by NF-κB inhibition. Thus, diabetes induces changes in PDL fibroblast gene expression that can enhance neutrophil recruitment and bone resorption, which may be explained by high glucose-induced NF-κB activation. Furthermore, PDL fibroblasts express a regulatory element in vivo that is typical of committed osteoblasts.

Objective: To investigate whether periodontitis, characterized by marginal jawbone loss, precedes the onset of symptoms of rheumatoid arthritis (RA), and to analyze plasma levels of RANKL (a cytokine that is crucial for bone resorption) and anti-citrullinated peptide antibodies (ACPAs) in presymptomatic individuals compared with matched referent controls., Methods: Marginal jawbone loss was measured on dental radiographs of the premolar/molar regions in the jaws in 176 subjects, 93 of whom subsequently developed RA. Among these participating subjects, 46 had documented radiographs predating symptom onset, and 45 cases could be matched to controls, according to sex, age, and smoking status. Plasma RANKL concentrations were analyzed using enzyme-linked immunosorbent assay. A receiver operating characteristic curve was used to define the cutoff value for RANKL positivity., Results: Bone loss was significantly greater in presymptomatic subjects classified as never smokers compared with that in controls, and increasing levels of bone loss were associated with a higher risk of the subsequent development of RA (hazard ratio 1.03, 95% confidence interval 1.01-1.05). No association between jawbone loss and RA was observed in smokers. A significantly greater extent of marginal jawbone loss was detected in RANKL-positive presymptomatic subjects, and even more pronounced jawbone loss was observed in those who were positive for both RANKL and ACPA., Conclusion: Marginal jawbone loss preceded the clinical onset of RA symptoms, but this was observed only in nonsmokers. Moreover, marginal jawbone loss was significantly greater in RANKL-positive presymptomatic subjects compared with RANKL-negative presymptomatic subjects and was highest in presymptomatic subjects positive for both ACPA and RANKL., (© 2017, American College of Rheumatology.)

Background and Objective: Interleukin-22 (IL-22), mainly produced by CD4+ T-helper subtypes and innate lymphoid cells at barrier surfaces, is found to involve in several diseases, including diabetes, rheumatoid arthritis, peri-implantitis and chronic rhinosinusitis with nasal polyps. The purpose of this study was to investigate histological changes and the levels of interleukin-22, interleukin-22 receptor 1 (IL-22R1) and interleukin-22-binding protein (IL-22BP) in experimental periodontitis., Material and Methods: Sixty male 8-week-old Sprague Dawley rats were randomly allocated to six groups of 10 rats each. In the periodontitis groups, experimental periodontitis was established and the rats were killed on days 3, 5, 7, 11 and 15 after ligation, while the rats without ligation were killed on day 0, representing the healthy control group (day 0 group). Histopathologic changes were detected by hematoxylin and eosin (H&E) staining, and alveolar bone loss was determined by micro-computed tomography (micro-CT). Tartrate-resistant acid phosphatase (TRAP) staining was used to investigate osteoclast formation. Real-time quantitative PCR (qPCR) and immunohistochemistry were used to investigate the expression and location of IL-22, IL-22R1 and IL-22BP in gingival tissues., Results: H&E staining showed increasingly severe destruction of the epithelial layer between day 3 and day 7, and the hyperplasia of pocket epithelium and the formation of periodontal pockets could be detected from day 11 to day 15. Micro-CT indicated an exponential increase in alveolar bone loss from day 3 to day 11 (P < .01). Bone resorption tended to be stationary after this period. TRAP staining showed that the number of multinucleate osteoclasts peaked at day 3 (P < .001, compared with day 0) and decreased at subsequent time points between day 5 and day 15. IL-22BP was expressed strongly under steady-state conditions in epithelial cells. IL-22-positive cells could be clearly observed both in the epithelial layer and around the lamina propria, whereas IL-22R1 was mainly localized in the epithelial layer of the damage period. Real-time qPCR revealed up-regulation of IL-22 and IL-22R1, as well as down-regulation of IL-22BP in gingival tissues during the destructive phase of periodontitis., Conclusion: This study shows the expression and localization of IL-22, IL-22R1 and IL-22BP, as well as the relevant histopathological alterations during the development of experimental periodontitis., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Periodontitis, an infective disease caused by oral pathogens and the intrinsic aging process, results in the destruction of periodontal tissues and the loss of alveolar bone. This study investigated whether Boesenbergia pandurata extract (BPE) standardized with panduratin A exerted anti-periodontitis effects, using an aging model representative of naturally occurring periodontitis. In aged rats, the oral administration of BPE (200 mg·kg -1 ·day -1 ) for 8 weeks significantly reduced the mRNA and protein expression of interleukin-1β, nuclear factor-kappa B, matrix metalloproteinase (MMP)-2, and MMP-8 in gingival tissues ( p < 0.01). In alveolar bone, histological analysis with staining and micro-computed tomography revealed the attenuation of alveolar bone resorption in the BPE-treated aged group, which led to a significant reduction in the mRNA and protein expression of nuclear factor of activated T-cells c1 (NFATc1), c-Fos, tartrate-resistant acid phosphatase, and cathepsin K ( p < 0.01). BPE not only increased the expression of osteoblast differentiation markers, such as alkaline phosphate, and collagen type I (COL1A1), but also increased the ratio of osteoprotegerin to RANKL. Collectively, the results strongly suggested that BPE is a natural resource for the prevention or treatment of periodontal diseases.

A 49-year-old woman with several missing and periodontically compromised teeth was referred to the orthodontic department of National Health Insurance Service Ilsan Hospital by the periodontic department for interdisciplinary treatment. Multiple posterior teeth had been extracted 10 days earlier. Her chief complaint was crowding of the anterior teeth, and she wanted to improve both esthetics and function. Orthodontic, periodontic, and prosthodontic treatments were undertaken in the proper timing and sequence with an interdisciplinary approach. As a result, improved periodontal health and a stable occlusion and vertical dimension were achieved. Although there were limited teeth and alveolar bone for anchorage, good esthetic and functional treatment results were obtained through the application of temporary anchorage devices and proper biomechanics., (Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Objectives: The accuracy of analogue and especially digital intra-oral radiography in assessing interdental bone level needs further documentation. The aim of this study was to compare clinical and radiographic bone level assessment to intra-surgical bone level registration (1) and to identify the clinical variables rendering interdental bone level assessment inaccurate (2)., Materials and Methods: The study sample included 49 interdental sites in 17 periodontitis patients. Evaluation methods included vertical relative probing attachment level (RAL-V), analogue and digital intra-oral radiography and bone sounding without and with flap elevation. The latter was considered the true bone level. Five examiners evaluated all radiographs., Results: Significant underestimation of the true bone level was observed for all evaluation methods pointing to 2.7 mm on average for analogue radiography, 2.5 mm for digital radiography, 1.8 mm for RAL-V and 0.6 mm for bone sounding without flap elevation (p < 0.001). Radiographic underestimation of the true bone level was higher in the (pre)molar region (p ≤ 0.047) and increased with defect depth (p < 0.001). Variation between clinicians was huge (range analogue radiography 2.2-3.2 mm; range digital radiography 2.1-3.0 mm)., Conclusion: All evaluation methods significantly underestimated the true bone level. Bone sounding was most accurate, whereas intra-oral radiographs were least accurate. Deep periodontal defects in the (pre)molar region were most underrated by intra-oral radiography., Clinical Relevance: Bone sounding had the highest accuracy in assessing interdental bone level.

Background: Nerve and its related factors in the occurrence and development of periodontitis are worthy of further study. Denervation research is a useful addition to nerve and innervation studies. The aim of this study is to establish a rat model of inferior alveolar nerve transection combined with ligature-induced periodontitis to elucidate the effects of denervation on ligature-induced rat periodontitis., Material and Methods: Sixty-four Wistar rats were distributed to the four groups randomly: ligation (L); denervation (D); ligation+denervation (LD); and normal (N) as control. A ligation-inducing rat experimental periodontitis model was established in the L and LD groups. Rats in the D and LD groups also underwent the transection of the right inferior alveolar nerve simultaneously. Four weeks after the operation, the mandibles were taken out for micro-computed tomography analysis. Osteoclast number was observed through TRAP staining. The gingival tissues around the first molars were homogenized and measured by enzyme-linked immunosorbent assay for interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Collagen fibers were observed using Picro-Sirius Red staining. Nuclear factor (NF)-κB p65 and IκBα phosphorylation and osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) ratio in the gingival tissues were detected by western blotting., Results: Denervation strongly promoted ligature-induced alveolar bone loss in the LD group. The alveolar bone loss of the LD group was significantly increased compared with the L group. Furthermore, denervation aggravated trabecular bone breakdown in the bone specific parameters, including percentage bone area, trabecular thickness and bone mineral density. Increased TRAP-positive osteoclasts were detected in alveolar bone of the LD group. More serious collagen fiber destructions and increased expressions of IL-1β and TNF-α were found in the LD group. NF-κB p65 and IκBα phosphorylation were also significantly upregulated in the LD group. OPG/RANKL ratio in the gingival extracts was markedly decreased in the LD group compared with the L group. Decreased OPG/RANKL ratio was observed in the D group, compared with the N group., Conclusion: Denervation effectively aggravates ligature-induced rat periodontitis by the NF-κB signaling pathway for excessive production of IL-1β and TNF-α and increased osteoclasts for decreased OPG/RANKL ratio. The rat model of inferior alveolar nerve transection that combined ligature-induced periodontitis provides an animal model to observe further the change of nerve-related factors in the occurrence and development of periodontitis, so as to select positive nerve-related factors to regulate inflammation and promote periodontal regeneration in the future., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: To identify phenotypes of periodontitis patients by the use of an unsupervised modelling technique (clustering), based on pre-treatment radiographic and microbiological characteristics., Materials and Methods: This retrospective study included data from 392 untreated periodontitis patients. Co-regularized spectral clustering algorithm was used to cluster the patients. The resulting clusters were subsequently characterized based on their demographics, radiographic bone loss patterns and microbial data., Results: The vast majority of patients fitted into one of the three main clusters (accuracy 90%). Cluster A (n = 18) was characterized by high prevalence and high proportions of Aggregatibacter actinomycetemcomitans, a trend for a more localized pattern of alveolar bone loss and young individuals. Clusters B (n = 200) and C (n = 135) differed clearly in disease severity patterns and smoking habits, but not in microbiological characteristics., Conclusion: On the basis of alveolar bone loss patterns and microbiological data, untreated periodontitis patients can be clustered into at least three phenotypes. These results should be validated in other cohorts, and the clinical utility needs to be explored on the basis of periodontal treatment outcomes and/or disease progression., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Intermittent administration of parathyroid hormone (PTH) has been demonstrated to have anabolic effects on bone metabolism and is approved for use in the treatment of osteoporosis. This study evaluates the role of intermittent PTH administration on alveolar bone loss in streptozotocin (STZ)-induced diabetic rats., Design: Fifty male Sprague Dawley rats were randomly divided into the following five groups: (1) a control group (saline placebo without ligature and STZ injection), (2) a PTH group (PTH administration without ligature and STZ injection), (3) an L group (saline placebo with ligature), (4) an L+STZ group (saline placebo with ligature and STZ injection), and (5) an L+STZ+PTH group (PTH administration with ligature and STZ injection). PTH was administered at 75μg/kg per dose four times a week for 28days. Subsequently, all rats were sacrificed, and their mandibles were extracted for micro-computed tomography (micro-CT) scanning, as well as histological and immunochemical evaluation., Results: Micro-CT scanning demonstrated the anabolic effect of PTH on alveolar bone metabolism in STZ-induced diabetic rats (P<0.05), and histomorphometry indicated that PTH inhibited inflammation of the periodontium and increased the level of osteoblastic activity (P<0.05). Immunochemical evaluation showed that rats subjected to both ligature placement and STZ injection had the highest receptor activator of nuclear factor kappa B ligand (RANKL)/osteoprotegerin (OPG) ratio and that PTH administration decreased this ratio., Conclusion: Intermittent systemic PTH administration effectively reduced alveolar bone loss and ameliorated the manifestation of experimental periodontitis in STZ-induced diabetic rats., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Clinical and radiographic examinations are essential in establishing correct periodontal diagnoses as well as providing appropriate treatment options. Current radiographic examinations, however, do not provide adequate information regarding the severity of periodontal disease, presenting a need to investigate alternative methods. The aim of this best evidence consensus is to determine when cone-beam computed tomography (CBCT) imaging is appropriate for diagnostic inquiry in the management of inflammatory periodontitis., Methods: Literature was systematically reviewed to answer three clinically relevant focused questions regarding the role of CBCT in the management of inflammatory periodontitis. 1) Clinical situation: In patients with periodontitis, what (if any) clinical situations/conditions exist where CBCT imaging improves diagnostic acumen and subsequent treatment recommendations compared with two-dimensional radiographic interpretation? 2) Intervention: Does CBCT imaging improve the accuracy of a diagnostic assessment and establishment of a prognosis in the analysis of furcation and/or intrabony defects? Is the execution of therapy improved and facilitated, or is it therapeutically challenged? 3) Outcomes: Does the use of CBCT imaging provide superior short-term or long-term clinical outcomes, more favorable patient-reported outcomes, or more consistent clinical treatment decisions affecting tooth prognosis (as measured by defect fill, improvements in bone anatomy, mobility patterns, and ultimate tooth survival)? An extensive literature search was performed using the MEDLINE database and the most respected journals in the field., Results: An electronic database search identified 885 citations, and a manual search yielded an additional five citations. After screening of article titles and abstracts, studies were excluded if irrelevant to the topic of this systematic review. Of the remaining full-text articles, 74 were obtained and reviewed. Sixty-two articles not meeting inclusion criteria were further excluded. Twelve total references met the inclusion criteria to determine the role of CBCT in diagnosis and treatment of both intrabony and furcation defects. Intrabony and furcation defects were the two most commonly discussed bony defects when comparing efficacy of CBCT versus intraoral radiographs (IRs). After a review of the literature, while diagnostic aspects of intrabony and furcation defects can be improved via the use of CBCT, limited evidence supported the use of CBCT imaging improving the execution of therapy for both types of defects. There was also a lack of literature to support the use of CBCT imaging for superior short-term or long-term clinical outcomes. None of the literature reported patient-reported outcomes when CBCT imaging was used., Conclusions: Currently, limited evidence supports the utilization of CBCT for diagnosis of intrabony and furcation defects. Despite the fact that there is rapidly accruing literature on CBCT, there are still no current evidence-based guidelines on its necessity and use for periodontal treatment planning. In selective cases, however, limited field of view CBCT may be useful for periodontal disease diagnoses due to less radiation dosage to the patient, higher spatial resolution, and shorter volumes to be interpreted.

Background and Objective: Periodontitis involves progressive loss of alveolar bone around the teeth. Hence, automatic alveolar bone loss measurement in periapical radiographs can assist dentists in diagnosing such disease. In this paper, we propose an automatic length-based alveolar bone loss measurement system with emphasis on a cementoenamel junction (CEJ) localization method: CEJ&#95;LG., Method: The bone loss measurement system first adopts the methods TSLS and ABLifBm, which we presented previously, to extract teeth contours and bone loss areas from periodontitis radiograph images. It then applies the proposed methods to locate the positions of CEJ, alveolar crest (ALC), and apex of tooth root (APEX), respectively. Finally the system computes the ratio of the distance between the positions of CEJ and ALC to the distance between the positions of CEJ and APEX as the degree of bone loss for that tooth. The method CEJ&#95;LG first obtains the gradient of the tooth image then detects the border between the lower enamel and dentin (EDB) from the gradient image. Finally, the method identifies a point on the tooth contour that is horizontally closest to the EDB., Results: Experimental results on 18 tooth images segmented from 12 periodontitis periapical radiographs, including 8 views of upper-jaw teeth and 10 views of lower-jaw teeth, show that 53% of the localized CEJs are within 3 pixels deviation (∼ 0.15 mm) from the positions marked by dentists and 90% have deviation less than 9 pixels (∼ 0.44 mm). For degree of alveolar bone loss, more than half of the measurements using our system have deviation less than 10% from the ground truth, and all measurements using our system are within 25% deviation from the ground truth., Conclusion: Our results suggest that the proposed automatic system can effectively estimate degree of horizontal alveolar bone loss in periodontitis radiograph images. We believe that our proposed system, if implemented in routine clinical practice, can serve as a valuable tool for early and accurate diagnosis of alveolar bone loss in periodontal diseases and also for assessing the status of alveolar bone following various types of non surgical and surgical and regenerative therapy. For overall system improvement, a more objective comparison by using transgingival bone measurement with a periodontal probe as the ground truth and enhancing the localization algorithms of these three critical points are the two major tasks., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Periodontal research involves the use of animal models to better understand the biological processes of periodontal diseases and the potential of new or existing therapies. Currently, ligature-induced periodontitis in rats is the main model used in periodontal research, in this model, alveolar bone loss (ABL) is the main parameter evaluated by radiographic, morphometric, and histological techniques. Interestingly, although these methodologies are widely used, it is not totally clarified neither the kinetics of ABL over the induction time nor the agreement degree (repeatability and reproducibility) of these techniques., Objective: To characterize ABL kinetics at 0, 3, 7, 15, 30, and 60 days after ABL induction by ligature and to evaluate the intra- (repeatability) and inter-examiner (reproducibility) agreement and the correlation among the radiographic, morphometric, and histological methodologies., Material and Methods: 60 male Wistar rats with induced ABL were randomly divided into 6 experimental groups (n = 10 animals/group). After 0, 3, 7, 15, 30, and 60 days, the animals were euthanized and their hemimandibles were removed for ABL determination using radiographic, morphometric and histological techniques., Results: Radiographic and morphometric/linear techniques allowed the detection of statistically significant ABL on the third day, while histological and morphometric/area techniques could only detect ABL after the seventh day (ANOVA/Tukey, p<0.05). After the fifteenth day, except for histological analysis, the ABL was stabilized. Concerning the agreement of the methodologies, Bland Altman's test (intra and inter-examiner evaluations) showed no difference among the measurements (p>0.05). In addition, high correlations (Pearson's test, r2>0.9, p<0.05) were observed., Conclusion: The results indicated that the minimum time for ABL induction could vary from 3 to 7 days, according to the chosen analysis methodology. Agreement and correlation data support the comparison of results between studies with same induction time.

Aim: To evaluate the effects of metformin (Met) on inflammation, oxidative stress, and bone loss in a rat model of ligature-induced periodontitis., Materials & Methods: Male albino Wistar rats were divided randomly into five groups of twenty-one rats each, and given the following treatments for 10 days: (1) no ligature + water, (2) ligature + water, (3) ligature + 50 mg/kg Met, (4) ligature + 100 mg/kg Met, and (5) ligature + 200 mg/kg Met. Water or Met was administered orally. Maxillae were fixed and scanned using Micro-computed Tomography (μCT) to quantitate linear and bone volume/tissue volume (BV/TV) volumetric bone loss. Histopathological characteristics were assessed through immunohistochemical staining for MMP-9, COX-2, the RANKL/RANK/OPG pathway, SOD-1, and GPx-1. Additionally, confocal microscopy was used to analyze osteocalcin fluorescence. UV-VIS analysis was used to examine the levels of malondialdehyde, glutathione, IL-1β and TNF-α from gingival tissues. Quantitative RT-PCR reaction was used to gene expression of AMPK, NF-κB (p65), and Hmgb1 from gingival tissues. Significance among groups were analysed using a one-way ANOVA. A p-value of p<0.05 indicated a significant difference., Results: Treatment with 50 mg/kg Met significantly reduced concentrations of malondialdehyde, IL-1β, and TNF-α (p < 0.05). Additionally, weak staining was observed for COX-2, MMP-9, RANK, RANKL, SOD-1, and GPx-1 after 50 mg/kg Met. OPG and Osteocalcin showed strong staining in the same group. Radiographically, linear measurements showed a statistically significant reduction in bone loss after 50 mg/kg Met compared to the ligature and Met 200 mg/kg groups. The same pattern was observed volumetrically in BV/TV and decreased osteoclast number (p<0.05). RT-PCR showed increased AMPK expression and decreased expression of NF-κB (p65) and HMGB1 after 50 mg/kg Met., Conclusions: Metformin, at a concentration of 50 mg/kg, decreases the inflammatory response, oxidative stress and bone loss in ligature-induced periodontitis in rats.

Aim: The aim was to retrospectively assess the age of onset of disease in a group of patients, 30-45 years of age, diagnosed with severe, generalised periodontitis., Material & Methods: Seventy-four patients agreed to be part of the study. Patient files and radiographs of 42 patients were retrieved from >80 private and public dental clinics. Interproximal sites in radiographs presenting with identifiable cement-enamel junction (CEJ) and alveolar bone crest (BC) were analysed. The distance between CEJ and BC was measured, and two thresholds were used; ≥3 mm and ≥5 mm. The lowest patient age at which a radiographic examination revealed a CEJ-BC distance of ≥3 mm (F3) and ≥5 mm (F5) at any site was recorded. Similarly, the highest patient age at which a radiographic examination revealed absence of sites with CEJ-BC ≥3 mm (L0) was assessed., Results: Complete sets of radiographs including periods prior to periodontal breakdown (L0) and disease stages F3, F5 and at recruitment were retrieved in 19 patients. Onset of disease, that is, the interval between L0 and F3, occurred on the average between 22.3 and 28.1 years of age and sites exhibiting severe bone loss (F5) were detected at the age of about 32.4 years., Conclusion: Severe, generalised periodontitis in 30- to 45-year-old subjects of the current sample commenced mainly between 22 and 28 years of age., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Objective: The potential benefits of statins in modulating periodontal disease is supported by in vitro and clinical studies showing statins can induce a lower expression of proinflammatory cytokines and matrix metalloproteinases. The aim of this study was to evaluate the effects of rosuvastatin (ST) on ligature-induced periodontitis in spontaneously hypertensive rats (SHR)., Material and Methods: Fifty-four adult male rats were divided into three groups: SHR-C, SHR-L and SHR-L-ST (C, control; L, ligature groups). In the SHR-L-ST group, animals were treated with daily 2 mg/kg ST administration. In L groups, a ligature remained around mandibular first molars for 10 d. Each group was divided for killing at 10 or 21 d postoperatively. Microtomographic and histometric analyses were performed. Osteoclastogenesis was evaluated by tartrate-resistant acid phosphatase assay and gene expression of 84 proinflammatory mediators by polymerase chain reaction array., Results: The SHR-L-ST group showed reduced bone loss and attachment loss in comparison with the SHR-L group at both 10 and 21 d postoperatively (p < 0.05). ST decreased the amount of tartrate-resistant acid phosphatase-positive cells compared with the SHR-L group at both 10 and 21 d (p < 0.05). The SHR-L-ST group presented 14 genes differentially expressed when compared with SHR-L group, featuring a downregulated gene profile at 10 d., Conclusion: Statin therapy may promote a protective effect against alveolar bone and connective tissue attachment losses attributable to periodontitis in hypertensive rats through inflammatory gene profile modulation., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Diabetes is a risk factor for periodontitis, an inflammatory bone disorder and the greatest cause of tooth loss in adults. Diabetes has a significant impact on the gut microbiota; however, studies in the oral cavity have been inconclusive. By 16S rRNA sequencing, we show here that diabetes causes a shift in oral bacterial composition and, by transfer to germ-free mice, that the oral microbiota of diabetic mice is more pathogenic. Furthermore, treatment with IL-17 antibody decreases the pathogenicity of the oral microbiota in diabetic mice; when transferred to recipient germ-free mice, oral microbiota from IL-17-treated donors induced reduced neutrophil recruitment, reduced IL-6 and RANKL, and less bone resorption. Thus, diabetes-enhanced IL-17 alters the oral microbiota and renders it more pathogenic. Our findings provide a mechanistic basis to better understand how diabetes can increase the risk and severity of tooth loss., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to evaluate low-level laser therapy (LLLT) as an adjuvant treatment for scaling and root planing (SRP) for the treatment of induced periodontitis in simvastatin-modified rats., Material and Methods: A total of 180 rats were evenly divided into two groups: Veh - receiving oral administration of polyethylene glycol (vehicle); S - receiving oral administration of Simvastatin. Periodontal disease was induced in both groups at the first mandibular molar. After seven days, the ligature was removed and the animals were divided into subgroups according to the following local treatments: NT - no treatment; SRP - scaling and root planing and irrigation with saline solution; and LLLT ¬- SRP and laser irradiation (660 nm; 0.03 W; 4 J). Ten animals in each subgroup/local treatment were euthanized at 7, 15 and 30 days. Samples of gingival tissue were processed to analyze the tissue oxidative damage and radiographic analysis. Levels of oxidative stress were analyzed by the expressions of Tripeptideglutathione (TG), Malondialdehyde (MDA) and Carbonylated Proteins (CP)., Results: The animals in S group had higher levels of TG and lower levels of MDA and CP compared with Veh group (p<0.05). Radiographically, in the intragroup analysis Veh and S, LLLT showed lower bone loss (BL) compared with NT and SRP, in all experimental periods (p<0.01). In addition, a lower BL was observed for the animals of Veh group treated with LLLT compared with treatment SRP in the S group, in all experimental periods., Conclusion: Within the limits of this study, we can conclude that LLLT was effective as adjuvant treatment for SRP protecting against the occurrence of oxidative tissue damages as well as for reducing alveolar bone loss in experimentally induced periodontitis simvastatin-modified rats.

Background: Osteoporosis and periodontitis have several risk factors in common. The majority of studies evaluating periodontal bone loss and systemic bone mineral density have found that low bone mineral density systemically is significantly associated with an increase in loss of alveolar bone height and periodontal destruction. Hence, the purpose of the study was to determine the effect of periodontitis on mandibular radiomorphometric indices, serum calcium and serum estradiol levels in postmenopausal women., Materials and Methods: Forty female patients in the age group of 35-55 years were included in the study. The participants were divided into two equal groups, i.e., control group A (twenty - postmenopausal women with healthy periodontium) and study group B (twenty - postmenopausal women with periodontitis). A thorough clinical examination of all the forty patients was carried out to detect the presence of periodontitis on the basis of clinical attachment level. Quantitative indices were measured on digital panoramic radiographs, and serum calcium and estradiol levels were estimated., Results: No statistically significant correlation of periodontitis with any of the radiomorphometric indices, serum calcium and serum estradiol levels was observed in postmenopausal women., Conclusion: There is little evidence of correlation of serum estradiol, serum calcium levels, and morphometric indices with periodontitis and therefore detailed further research about this correlation is required.

Background: This study aims to evaluate the ameliorative effect of carvacrol, an anti-inflammatory monoterpenoid phenol and a major component of Plectranthus amboinicus, on periodontal damage in an experimental rat model of periodontitis., Methods: Forty Sprague-Dawley rats were divided into ligation (Lig), non-ligation (n-Lig), and two ligation plus carvacrol (Lig+C) groups. Carvacrol (17.5 or 35.0 mg/kg body weight/day) was administered intragastrically from 1 day before ligation. On day 8, dental alveolar bone loss and gingival inflammation in periodontal specimens were examined by dental radiography, microcomputed tomography, and histology. Expressions of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and inducible nitric oxide synthase messenger (m)RNAs, and levels of matrix metalloproteinase (MMP)-2 and MMP-9 in gingiva were examined by reverse transcription-polymerase chain reaction and zymography., Results: Dental radiography revealed periodontal bone-supporting ratios in Lig and Lig+C groups were lower than the n-Lig group, with Lig group ratios being lowest. Compared with the n-Lig group, the cemento-enamel junction-bone distance was significantly longer in Lig and Lig+C groups, with Lig+C groups showing shorter distances regardless of radiographic methods used. Histology and histometry showed less inflammatory area and stronger connective tissue attachment in Lig+C groups than in the Lig group. Cytokine/mediator mRNA expression and MMP-9 levels were reduced in the Lig+C groups., Conclusions: Carvacrol reduced tissue damage and bone loss caused by ligation-induced periodontitis. The present results indicate that carvacrol might reduce tissue destruction by downregulating expression of proinflammatory mediators and MMP-9.

Background: The aim of this study was to present and validate a novel procedure for the quantitative volumetric assessment of extraction sockets that combines cone-beam computed tomography (CBCT) and image processing techniques., Methods: The CBCT dataset of 9 severely resorbed extraction sockets was analyzed by means of two image processing software, Image J and Mimics, using manual and automated segmentation techniques. They were also applied on 5-mm spherical aluminum markers of known volume and on a polyvinyl chloride model of one alveolar socket scanned with Micro-CT to test the accuracy., Results: Statistical differences in alveolar socket volume were found between the different methods of volumetric analysis (P<0.0001). The automated segmentation using Mimics was the most reliable and accurate method with a relative error of 1.5%, considerably smaller than the error of 7% and of 10% introduced by the manual method using Mimics and by the automated method using ImageJ., Conclusions: The currently proposed automated segmentation protocol for the three-dimensional rendering of alveolar sockets showed more accurate results, excellent inter-observer similarity and increased user friendliness. The clinical application of this method enables a three-dimensional evaluation of extraction socket healing after the reconstructive procedures and during the follow-up visits.

Epoxyeicosatrienoic acids (EETs), metabolites of arachidonic acid derived from the cytochrome P450 enzymes, are mainly metabolized by soluble epoxide hydrolase (sEH) to their corresponding diols. EETs but not their diols, have anti-inflammatory properties, and inhibition of sEH might provide protective effects against inflammatory bone loss. Thus, in the present study, we tested the selective sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), in a mouse model of periodontitis induced by infection with Aggregatibacter actinomycetemcomitans Oral treatment of wild-type mice with TPPU and sEH knockout (KO) animals showed reduced bone loss induced by A. actinomycetemcomitans This was associated with decreased expression of key osteoclastogenic molecules, receptor activator of nuclear factor-κB/RANK ligand/osteoprotegerin, and the chemokine monocyte chemotactic protein 1 in the gingival tissue without affecting bacterial counts. In addition, downstream kinases p38 and c-Jun N-terminal kinase known to be activated in response to inflammatory signals were abrogated after TPPU treatment or in sEH KO mice. Moreover, endoplasmic reticulum stress was elevated in periodontal disease but was abrogated after TPPU treatment and in sEH knockout mice. Together, these results demonstrated that sEH pharmacological inhibition may be of therapeutic value in periodontitis., (Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.)

Contemporary periodontal therapy has evolved to become more interdisciplinary and increasingly involves more complex treatments, including bone and soft-tissue regenerative procedures. Therapeutic options require an imaging modality or combination of techniques that are capable of providing a diagnostic osseous baseline and facilitating quantification of smaller increments of bony change, both loss and additive, which are comparable over time. Intra-oral and panoramic radiography are the modalities most commonly used to identify the location, quantify the amount and the pattern of alveolar bone loss and determine response to therapy. Cone-beam computed tomography imaging offers specific advantages for periodontal diagnosis in that three-dimensional images of dental and alveolar bone structures can be rendered with accuracy. Cone-beam computed tomography has been shown to be clinically efficacious in demonstrating localized defects, such as furcation involvement and intrabony vertical and buccal/lingual defects, and in assessing the effects of regenerative therapy. In these situations, limited-field-of-view, high-resolution protocols are indicated., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)