Role of ferroptosis in periodontitis: An animal study in rats.

OBJECTIVE: This study aimed to investigate (1) the temporal pattern of ferroptosis, an iron-dependent cell death, in ligation-induced rat periodontitis and (2) the effect of ferrostatin-1, a ferroptosis inhibitor, on the model. BACKGROUND: Ferroptosis may contribute to various diseases. However, the role of ferroptosis in periodontitis is still fully understood. METHODS: In the first experiment, 25 rats with ligation-induced periodontitis were sacrificed on days 0, 1, 2, 7, and 10. Gingivae were obtained to determine tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and ferroptotic biomarkers, including solute carrier family 3 member 2 (SLC3A2) and solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (Gpx4), via immunoblotting. Using microcomputed tomography (µCT) and histology, the periodontal soft and hard tissue lesions, including dental alveolar bone crest level, bony characteristics of the surrounding alveolus, periodontal tissue inflammation, and periodontal tissue losses, were evaluated. In study two, 16 rats with induced periodontitis were grouped according to ferrostatin-1 treatment. The rats were intraperitoneally injected with solvent or ferrostatin-1 (1.5 mg/kg/day) 1 day before ligation and sacrificed on days 7 and 10. Gingival protein changes and periodontal tissue damage were also examined. RESULTS: In study one, SLC3A2/SLC7A11 and Gpx4 decreased since day 1; however, TNF-α/IL-1ß increased on days 7 and 10. Moreover, the µCT/histology revealed resorptive bony characteristics, inflamed gingival tissue, and periodontal attachment loss. In study two, ferrostatin-1-injected rats exhibited significantly increased SLC3A2/SLC7A11 and Gpx4 but decreased TNF-α/IL-1ß than vehicle rats. They also revealed lessened bone resorption, tissue inflammation, and attachment loss. CONCLUSION: This study highlights the role of ferroptosis, via the system Xc/Gpx4 pathway, in experimental periodontitis and may serve as a regulatory strategy.

Life satisfaction and peace of mind among dentists: a cross-sectional study.

OBJECTIVES: This study sought to identify the factors associated with the life satisfaction and peace of mind (PoM) of dentists not in full-time clinical training. MATERIALS AND METHODS: Cross-sectional questionnaires were distributed to dentists in Taiwan to collect their life satisfaction, PoM, sociodemographic data, and dental career-related characteristics. Life satisfaction was measured using a 5-item Satisfaction with Life Scale. PoM was measured using a 7-item Peace of Mind Scale. Descriptive statistics and multiple linear regression models were estimated to explore potential associations between the two scales and the examined factors. RESULTS: A total of 1196 dentists (45.6% female; mean age = 44.12) completed the questionnaires. The response rate of completed questionnaires from email invitations was 32.9%. On multivariable analysis, life satisfaction and PoM were associated with age (b = 0.008 in both), better perceived health (b = 0.262 and 0.308, respectively), family interaction (b = 0.264 and 0.207, respectively), and friend relationships (b = 0.076 and 0.091, respectively). Being married (b = 0.191), being specialized (b = 0.127), working in private practice, and spending 10 to 39 h per week with patients (b = 0.101 to 0.162) were associated with a higher level of life satisfaction but not PoM. CONCLUSIONS: Specialists working in private practice without working overtime were associated with better life satisfaction. However, the dentists' health and relationships with family were more related to their subjective well-being than their professional achievements. CLINICAL RELEVANCE: Our findings can help policymakers increase awareness of the well-being of general dentists and those in academia or hospitals to promote their mental health.

Is periodontitis a risk factor of benign or malignant colorectal tumor? A population-based cohort study.

OBJECTIVE: To examine the risk of developing benign or malignant colorectal tumors in patients with periodontitis within 15 years using Taiwan's National Health Insurance Database. BACKGROUND: Studies have shown that colorectal carcinoma often develops under inflammatory conditions and changes of microbiota in the gut. Recently, a link between Fusobacterium nucleatum, a periodontal pathogen, and colorectal carcinoma has been proposed. However, whether periodontitis is a risk of developing colorectal tumor remains uncertain. METHODS: In total, 35 124 participants were enrolled from 2000 to 2015 to examine the development risk of benign colorectal tumors, including 11 708 patients with periodontitis who received therapy (group 1), 11 708 patients with periodontitis not receiving periodontal treatment (group 2), and 11 708 non-periodontitis controls after matching for gender, age, and index year. To examine the risk of developing colorectal malignancy, 11 720 participants were assigned to each of the three groups. Cox proportional hazards model and Kaplan-Meier methods were used to compare the risks. Sensitivity analysis was performed, excluding the diagnoses during the first 1 or 5 years. RESULTS: After the follow-up, 177, 154, and 63 participants in group 1, group 2, and control group had benign colorectal tumors. Patients with periodontitis tended to be associated with a greater rate of having a benign colorectal tumor. The adjusted hazard ratios (aHRs) were 3.77 (95% confidence interval [CI] 2.01-4.82, p < .001) and 2.85 (95% CI 1.62-3.74, p < .001) for groups 1 and 2, respectively. Regarding the risk of malignant colorectal tumor, 20, 18, and 14 participants who developed malignant tumors were included in group 1, group 2, and control group; however, no significant increase in malignancy was observed in periodontitis groups (aHR1.92, 95% CI 0.74-2.36, p = .482; aHR 1.50, 95% CI 0.68-1.97, p = .529, for the two periodontitis groups, respectively). CONCLUSIONS: The results of this study suggest that patients with periodontitis may have an increased risk of developing benign, but not malignant, colorectal tumors.

Association of periodontitis with tinnitus: A population-based cohort study in Taiwan.

AIM: Tinnitus, ringing in the ears, is speculated to be driven by inflammation. This study examined whether periodontitis is a risk factor for tinnitus using Taiwan's National Health Insurance Research Database. MATERIALS AND METHODS: Among the 79,456 patients who visited for dental concerns, 11,055 patients who were diagnosed with periodontitis and underwent periodontal treatment between 2000 and 2015 were enrolled in Group 1. After matching for sex, age, and index year, 11,055 patients with periodontitis who received no treatment were enrolled in Group 2. Similarly, 11,055 participants without periodontitis were included as controls. RESULTS: At the end of the follow-up, 412 and 404 participants in the two periodontitis groups and 321 participants in the control group had tinnitus. Cumulative risk for tinnitus in Group 1 or 2 was significantly greater than in the control group. More periodontitis patients than controls developed tinnitus (adjusted hazard ratios were 1.71 (95% confidence interval [CI]: 1.49-1.97, p < .001) and 1.64 (95% CI: 1.37-1.86, p < .001) in Groups 1 and 2, respectively). The risks were not significantly different between Groups 1 and 2. Similar findings were obtained after excluding data for the first 1 or 5 years. CONCLUSIONS: The study findings indicate that periodontitis is associated with tinnitus.

Antioxidants protect against gingival overgrowth induced by cyclosporine A.

OBJECTIVE: We investigated the importance of reactive oxygen species (ROS) on developing gingival overgrowth (GO) and then introduced the antioxidant strategy to prevent, or even reduce GO. BACKGROUND: Gingival overgrowth is a common side effect of the patients receiving cyclosporine A (CsA), an immune suppressant. Although it has been broadly investigated, the exact pathogenesis of the induced GO is still uncertain. METHODS: We cultured human primary gingival fibroblasts and used animal model of GO to investigate the ameliorative effects of antioxidants on CsA-induced GO. To examine the CsA-induced oxidative stress, associated genes and protein expression, and the overgrown gingiva of rats by using immunocytochemistry, confocal laser scanning microscopy, real-time PCR, ELISA, gelatin zymography, gingival morphological, and immunohistochemical analysis. RESULTS: We found for the first time that ROS was responsible for the CsA-induced oxidative stress and TGF-ß1 expression in human primary gingival fibroblasts, as well as the GO of rats. The antioxidants (oxidative scavenger of vitamin E and an antioxidative enzyme inducer of hemin) ameliorated CsA-induced pathological and morphological alterations of GO without affected the CsA-suppressed il-2 expression in rats. CsA-induced oxidative stress, HO-1, TGF-ß1, and type II EMT were also rescued by antioxidants treatment. CONCLUSIONS: We concluded that CsA repetitively stimulating the production of ROS is the cause of CsA-GO which is ameliorated by treating antioxidants, including vitamin E and sulforaphane. Furthermore, the immunosuppressive effect of CsA is not interfered by antioxidant treatments in rats. This finding may thus help the clinician devise better prevention strategies in patients susceptible to GO.

Fibroblast-enhanced cyclophilin A releasing from U937 cell upregulates MMP-2 in gingival fibroblast.

OBJECTIVE: This in vitro study aimed to evaluate the expression of cyclophilin A (CyPA) in U937 monocytic cells after coculturing with the human gingival fibroblasts (HGFs) and the effect of CyPA on the augmentation of MMP-2 expression in the coculture environment. BACKGROUND: Leukocyte infiltration in gingival connective tissue is one of the major findings in the lesions of inflammatory periodontal diseases. A crosstalk between the resident gingival fibroblasts and the recruited inflammatory cells that promote the expression of matrix metalloproteinases (MMPs) was proposed based on recent findings, whereas the cluster of differentiation 147 (CD147)-CyPA pathway was suggested to be involved with the crosstalk. MATERIAL AND METHODS: CyPA was released into media, in the independent or transwell coculture of HGF and U937 cells, as determined by enzyme-linked immunosorbent assay, whereas intracellular mRNA expressions for CyPA and MMP-2 were examined by quantitative real-time polymerase chain reaction, in the transwell coculture or conditional medium models. Zymography was conducted to analyze the activities of pro-MMP-2/MMP-2 released into the media. RESULTS: (a) A significantly increased CyPA protein level was observed in the transwell coculture media compared with that in the independent culture. (b) The transwell coculture-enhanced mRNA expression for CyPA was noticed in U937 cells but not in HGFs. After adding with HGF-conditioned medium, the mRNA enhancement in U937 cells occurred in a dose-dependent manner. (c) Although the MMP-2 activities significantly increased after transwell coculturing, the MMP-2 mRNA enhancement was observed only in HGFs. (d) Exogenous CyPA could enhance MMP-2 activities in HGFs in a dose-dependent manner. However, the CyPA antagonist reduced the MMP-2 activities in the transwell cocultures. (e) Moreover, the CyPA-enhanced MMP-2 activity in HGF was decreased significantly by the pathway inhibitor for c-Jun amino-terminal kinase (JNK). CONCLUSION: Based on the present findings, we suggest that gingival fibroblasts could enhance the CyPA release from U937 cells, via the JNK pathway, resulting in MMP-2 enhancement in fibroblasts. The finding shed light on a new mechanism of cellular interaction involving MMP-2 and CyPA, in two cells.

Association between periodontitis and pulmonary function based on the Third National Health and Nutrition Examination Survey (NHANES III).

OBJECTIVES: The purpose of this study was to investigate the association between impaired pulmonary function and periodontitis. MATERIALS AND METHODS: From the Third National Health and Nutrition Examination Survey data, we examined the association between pulmonary function and severity of periodontitis using the univariate and multivariate regression models. Moreover, the association between obstructive or restrictive spirometry patterns and periodontitis status was also determined by multivariable logistic regression analysis. RESULTS: A total of 10,645 participants were included in our study. The values of predicted FEV1%, predicted FVC%, and FEV1/FVC were found to gradually decline with increasing severity of periodontitis (p < .001). Obstructive and restrictive pulmonary functions were significantly associated with severity of periodontitis. CONCLUSION: Individuals with a greater degree of periodontitis had poor pulmonary function. However, further long-term cohort studies are required for a comprehensive evaluation.

Life satisfaction of Taiwanese dental graduates received residencies in the U.S.: a cross-sectional study.

BACKGROUND: Each year, more than 200 international dental graduates start U.S. specialty trainings to become specialists. It is unknown if their life satisfaction is associated with any dental career-related factor before residencies (e.g. dental school class rank, research experience, or private practice experience) and after residencies (e.g. staying in the U.S., teaching status, workplace, or board certification). This cross-sectional study aimed to identify these potential factors by surveying Taiwanese dental graduates who pursued U.S. residencies. METHODS: Life satisfaction was measured with a structured questionnaire, Satisfaction With Life Scale (SWLS), which includes five statements on a 5-point Likert scale. Online surveys were sent out to 290 Taiwanese dental graduates who were known to pursue U.S. residencies. T-test, one way analysis of variance, and multivariable adjusted generalized linear model (GLM) were used to assess the differences of mean SWLS scores from different variables. RESULTS: Surveys were completed by 158 dentists. Mean SWLS score of 125 specialists was higher (p = 0.0007) than the score of 33 residents. For the 125 specialists, multivariable adjusted GLM demonstrated better life satisfaction was positively associated with multiple independent factors, such as having research experience, being ranked in the top 26 ~ 50% of the class in dental school, starting U.S. residency within 4 years after dental school, starting residency before year 1996, and specializing in endodontics (vs. periodontics). Life satisfaction was not associated with any factors after residency (e.g. staying in the U.S. afterwards, teaching status, or workplace), but better mean life satisfaction score was significantly associated with being American specialty board certified (p < 0.001) for the specialists in the 26 ~ 75% of their class in dental school. For the 33 residents, better mean life satisfaction score was associated with better dental school class rank in both bivariate (p = 0.020) and multivariable adjusted GLM (p = 0.004) analyses. CONCLUSIONS: The life satisfaction of Taiwanese dental graduates pursuing U.S. residencies might be associated with some professional factors, such as research experience, dental school class rank, residency timing, specialty type, and specialty board certification. We hope our results may provide some objective information on making career decisions for international dental graduates/students who are preparing for U.S. residency.

Bone Formation Using Cross-Linked Chitosan Scaffolds in Rat Calvarial Defects.

PURPOSE: To investigate the osteoconductive effect of a chitosan scaffold in a rat skull defect model. Previous publications have demonstrated the osteoinductive properties as scaffold materials with growth factors; however, whether chitosan alone has osteoconductive ability is unclear. This study used cross-linked chitosan scaffolds for in vivo evaluation of scaffold-supported bone regeneration in rat calvarial defects using histopathological analysis and examination of alkaline phosphatase (ALP), calcium, phosphorus, and calcitonin serum levels. MATERIALS AND METHODS: Scaffolds were made of cross-linked chitosan. After the defect was filled with the scaffold, the periosteum was carefully repositioned and sutured to stabilize the scaffold. The effects of the scaffold on wound repair were examined microscopically. Morphological radiographic and histopathological analyses of wound repair ratios were performed at 3 and 4 weeks after the defects were made. RESULTS: Using the cross-linked chitosan biomaterial of the wounds. The amount of regenerated bone measured was significantly greater in the chitosan-treated group than in the control group. The ALP level in the chitosan group at 4 weeks was higher than at baseline and at the 4-week follow-up in the control group (P < 0.05). CONCLUSIONS: The results show that cross-linked chitosan has an osteoconductive effect on bone regeneration in vivo.

Leptin OB3 peptide suppresses leptin-induced signaling and progression in ovarian cancer cells.

BACKGROUND: Obesity and its comorbidities constitute a serious health burden worldwide. Leptin plays an important role in diet control; however, it has a stimulatory potential on cancer cell proliferation. The OB3 peptide, a synthetic peptide, was shown to be more active than leptin in regulating metabolism but with no mitogenic effects in cancer cells. METHODS: In this study, we investigated the proliferative effects, gene expressions and signaling pathways modulated by leptin and OB3 in human ovarian cancer cells. In addition, an animal study was performed. RESULTS: Leptin, but not OB3, induced the proliferation of ovarian cancer cells. Interestingly, OB3 blocked the leptin-induced proliferative effect when it was co-applied with leptin. Both leptin and OB3 activated the phosphatidylinositol-3-kinase (PI3K) signal transduction pathway. In addition, leptin stimulated the phosphorylation of signal transducer and activator of transcription-3 (STAT3) Tyr-705 as well as estrogen receptor (ER)α, and the expression of ERα-responsive genes. Interestingly, all leptin-induced signal activation and gene expressions were blocked by the co-incubation with OB3 and the inhibition of extracellular signal-regulated kinase (ERK)1/2. Coincidently, leptin, but not OB3, increased circulating levels of follicle-stimulating hormone (FSH) which is known to play important roles in the initiation and proliferation of ovarian cancer cells. CONCLUSIONS: In summary, our findings suggest that the OB3 peptide may prevent leptin-induced ovarian cancer initiation and progression by disrupting leptin-induced proliferative signals via STAT3 phosphorylation and ERα activation. Therefore, the OB3 peptide is a potential anticancer agent that might be employed to prevent leptin-induced cancers in obese people.

2,3,5,4'-Tetrahydroxystilbene-2-O-ß-glucoside Isolated from Polygoni Multiflori Ameliorates the Development of Periodontitis.

Periodontitis, a chronic infection by periodontopathic bacteria, induces uncontrolled inflammation, which leads to periodontal tissue destruction. 2,3,5,4'-Tetrahydroxystilbene-2-O-beta-glucoside (THSG), a polyphenol extracted from Polygoni Multiflori, reportedly has anti-inflammatory properties. In this study, we investigated the mechanisms of THSG on the Porphyromonas gingivalis-induced inflammatory responses in human gingival fibroblasts and animal modeling of ligature-induced periodontitis. Human gingival fibroblast cells were treated with lipopolysaccharide (LPS) extracted from P. gingivalis in the presence of resveratrol or THSG to analyze the expression of TNF-α, IL-1ß, and IL-6 genes. Increased AMP-activated protein kinase (AMPK) activation and SirT1 expression were induced by THSG. Treatment of THSG decreased the expression of LPS-induced inflammatory cytokines, enhanced AMPK activation, and increased the expression of SirT1. In addition, it suppressed the activation of NF-κB when cells were stimulated with P. gingivalis LPS. The anti-inflammatory effect of THSG and P. Multiflori crude extracts was reproduced in ligature-induced periodontitis animal modeling. In conclusion, THSG inhibited the inflammatory responses of P. gingivalis-stimulated human gingival fibroblasts and ameliorated ligature-induced periodontitis in animal model.

Clinical and Microcomputed Topography Evaluation of the Concentrated Growth Factors as a Sole Material in a Cystic Bony Defect in Alveolar Bone Followed by Dental Implantation: A Case Report.

Concentrated growth factors (CGFs) can be used to enhance wound healing. This case report describes a short-term effect of CGF grafting followed by implant placement in a cystic bony defect within the mandible. Healing conditions were monitored by 2 implant-related surgeries, radiographs, and a microcomputed topography examination. Continuous increase of radiopacity in radiographs was noticed till 6 months after grafting. Bone core specimen was taken at 3.5 months after grafting, and percent bone volume reached 32.7% analyzed by microcomputed topography. In conclusion, the present case showed bone regeneration in the cystic bony defect grafted by CGFs alone.

Role of Shh and TGF in cyclosporine-enhanced expression of collagen and α-SMA by gingival fibroblast.

OBJECTIVE: Cyclosporine-A (CsA)-induced gingival overgrowth may arise from an alteration in stoma matrix homeostasis. Sonic hedgehog (Shh) plays a key role during embryogenic development and fibrotic progression, and may be involved in CsA-altered gingival matrix homeostasis. METHODS: Using the reverse transcription-polymerase chain reaction and Western blot analysis, we investigated the mRNA and protein expressions of Shh, type 1 collagen (COL1), alpha-smooth muscle actin (α-SMA) and transforming growth factor-beta (TGF-ß) in human gingival fibroblasts after CsA treatments. The effect of Shh on CsA-induced alterations was further evaluated by the extra-supplement or inhibition of Shh or TGF-ß. RESULTS: Cyclosporine-A enhanced COL1, α-SMA, Shh and TGF-ß expressions in human gingival fibroblasts. The exogenous Shh/TGF-ß augmented the expression of COL1 and α-SMA, and the Shh/TGF-ß inhibition suppressed the CsA-enhanced COL1 and α-SMA expressions. Moreover, Shh mRNA and protein expressions increased if extra-supplementing the exogenous TGF-ß, whereas the CsA-upregulated Shh was mitigated by the TGF-ß pathway inhibitor. However, neither exogenous Shh nor the Shh pathway inhibitor alters TGF-ß expression or CsA-up-regulated TGF-ß expression. CONCLUSIONS: Shh, regulated by TGF-ß, mediates CsA-altered gingival matrix homeostasis.

Selective cytotoxic effects of low-power laser irradiation on human oral cancer cells.

BACKGROUND AND OBJECTIVES: Low-power laser irradiation (LPLI) is known to regulate cell proliferation and migration in clinical use. Recent studies have shown that LPLI induces cell death in some certain types of cancer cell lines. However, the cytotoxic selectivity of LPLI for cancer cells is not fully understood. The aim of this study was to compare the cytotoxic effects of LPLI in both human oral cancer OC2 cells and normal human gingival fibroblast (HGF) cells. MATERIALS AND METHODS: LPLI at 810 nm with an energy density from 10 to 60 J/cm(2) was used to irradiate human oral cancer OC2 cells and normal HGF cells. RESULTS: We found that LPLI significantly diminished cell viability of human oral cancer OC2 cells due to cell cycle arrest at the G1 phase and the induction of cell death but that it had no or little effects on cell cycle progression and death in normal HGF cells. Moreover, the production of reactive oxygen species (ROS) and the loss of mitochondrial membrane potential (MMP) were elevated in human oral cancer OC2 cells compared with the un-irradiated cells. In contrast, these effects remained unchanged in normal HGF cells after exposure to LPLI. LPLI also induced apoptosis in caspase-3 dependent manner in human oral cancer OC2 cells, a mode of action that could be mediated by ROS and mitochondrial damage. CONCLUSION: Our findings imply LPLI might be a potential therapy for oral cancers.

The association between temporomandibular disorders and joint hypermobility syndrome: a nationwide population-based study.

OBJECTIVES: This study aims to investigate the risk factors of temporomandibular disorders (TMDs), including disc or non-disc-related disorders, and joint hypermobility syndrome (JHS) retrospectively and to analyze the factors by estimating the magnitude of the association between the two conditions using a nationwide population-based dataset. MATERIALS AND METHODS: A total of 975,788 eligible patients' de-identified data were obtained from a representative database composed of one million of Taiwan's population since 2004 to 2008. All associated factors, such as gender, age, facial trauma, and psychosis, which correlated with TMDs and JHS were examined. Multiple logistic regression modeling adjusted for confounding variables to determine the odds ratio of variables that made an important contribution to TMDs and JHS. RESULTS: For all TMDs patients, only 1.47% patients had disc-related disorders. For all JHS patients, only 3.85% patients are diagnosed with concomitant TMDs. Statistically significant association was observed between joint hypermobility and TMDs. Furthermore, the prevalence of JHS patients shows significant difference within TMD subgroups, in which 9.52% of JHS patients have disc disorders and 90.48% of JHS patients do not. All associated factors, such as gender, age, JHS, facial trauma, and psychosis, had a significant impact on the TMDs. Interestingly, patients with TMJ articular disc disorders are 6.7 times more likely to be diagnosed with JHS compared to patients without disc-related disorders. CONCLUSIONS: Our results confirm that there is a significant positive association between TMDs and JHS, highlighting that patients with disc-related TMDs are more likely to experience JHS than patients with TMDs without disc disorders. CLINICAL RELEVANCE: Individuals with TMD associated with JHS should be carefully evaluated by inter-disciplinary specialists as these factors may eventually have impact on the prognosis of TMDs and JHS.

Bifid mandibular canals and the factors associated with their presence: a medical computed tomography evaluation in a Taiwanese population.

OBJECTIVES: To examine distribution of bifid mandibular canals in a Taiwanese population and to evaluate factors contributing to the phenomenon. MATERIAL AND METHODS: Computed tomographic images from 173 subjects (97 females and 76 males) were obtained using a 64-slice multidetector computerized tomography system, and the presence of bifid mandibular canals, as well as their widths and lengths, was examined. Association of length of bifid canals with possible contributing factors, including gender, age, and side of presentation, as well as size of cross-sectional bony area of mandible along the long axis of mandibular canal, was evaluated. RESULTS: Bifid mandibular canals, with mean values of 10.1 and 0.9 mm in length and width, were found in 53 (30.6%) of 173 patients and 64 (18.5%) of 346 hemi-mandibles. Bifid canals appeared more frequently and tend to penetrate mandible with greater lengths in males if compared with those in females. When males were compared with females and when mandibles with bifid canals were compared with ones without, the former tend to present with larger bony area at corresponding levels of cross-sectional plane than the later, respectively. By regression analysis, significant association was found between length of bifid canals and gender, side of hemi-mandible, and bony area at mid-zone of mandibular canal. CONCLUSIONS: Bifid canals were observed in 30.6% of subjects and 18.5% of hemi-mandibles. Significant association between length of bifid canals and gender, side of hemi-mandible, and cross-sectional bony area of mandible was observed.

Periodontal repair in dogs: space-provision supports alveolar bone and cementum formation.

OBJECTIVE: Clinical criteria for periodontal wound healing/regeneration include wound stability, space-provision and conditions for primary intention healing. However, wound stability/space-provision may be difficult to obtain in non-contained periodontal defects. The objective of this study was to; using a limited, space-providing device as a conduit, evaluate a concept of space-provision sans tissue occlusion for periodontal wound healing/regeneration. METHODS: Bilateral, critical-size, supraalveolar, periodontal defects were created in eight young adult Beagle dogs. One jaw quadrant received a limited, space-providing titanium mesh device, the contra-lateral jaw quadrant served as sham-surgery control followed by submerged wound closure for primary intention healing. The animals were euthanized at 8 weeks for histometric analysis of the surgical sites. RESULTS: Clinical healing was generally uneventful; minor late exposures observed for some defects. Experimental sites exhibited significantly enhanced mean (±SE) bone and cementum regeneration compared with control (1.10 ± 0.20 and 1.32 ± 0.10 mm versus 0.34 ± 0.18 and 0.66 ± 0.15 mm; p < 0.01). A cellular mixed (extrinsic/intrinsic) fibre cementum and functionally oriented collagen fibres were routinely observed. Wound exposures were significantly associated with reduced bone formation (p < 0.05). CONCLUSIONS: Using a limited, space-providing device to support periodontal wound healing/regeneration appears a promising clinical approach for non-contained periodontal defects.

Effects of bone morphogenetic protein-6 on periodontal wound healing/regeneration in supraalveolar periodontal defects in dogs.

OBJECTIVE: Application of a synthetic BMP-6 polypeptide in a rat periodontal fenestration defect model enhanced periodontal wound healing/regeneration including new bone and cementum formation. The purpose of this study was to translate the relevance of these initial observations into a discriminating large animal model. METHODS: Critical-size (4-5 mm) supraalveolar periodontal defects were created at the 2(nd) and 3(rd) mandibular premolar teeth in 11 Beagle dogs. Experimental sites received BMP-6 at 0.25, 1.0 and 2.0 mg/ml soak-loaded onto an absorbable collagen sponge (ACS) carrier or ACS alone (control) each condition repeated in four jaw quadrants. The animals were euthanized at 8 weeks when block biopsies were collected and processed for histologic/histometric analysis. RESULTS: BMP-6 at 0.25, 1.0 and 2.0 mg/ml soak-loaded onto the ACS yielded significantly enhanced new bone (0.99 ± 0.07 versus 0.23 ± 0.13 mm/BMP-6 at 0.25 mg/ml) and cementum (2.45 ± 0.54 versus 0.73 ± 0.15 mm/BMP-6 at 0.25 mg/ml) formation including a functionally oriented periodontal ligament compared with control (p < 0.05). A significant inverse linear association between BMP-6 dose and new bone (ß = -0.21 ± 0.09 mm, p = 0.016) and cementum height (ß = -0.34 ± 0.15 mm, p = 0.023) was observed. Minimal root resorption was observed without significant differences between groups. Ankylosis was not observed for any of the experimental groups. CONCLUSIONS: Surgical application of BMP-6/ACS onto critical-size supraalveolar defects enhanced periodontal wound healing/regeneration, in particular cementogenesis including a functionally oriented periodontal ligament; the low BMP-6 0.25 mg/ml concentration apparently providing the most effective dose.

Can chlorhexidine mouthwash twice daily ameliorate cyclosporine-induced gingival overgrowth?

BACKGROUND/PURPOSE: Gingival overgrowth can be induced in patients treated with cyclosporine-A (CsA), an immunosuppressant often used following organ transplantation. A pre-existing rat model designed to mimic CsA-induced gingival overgrowth in humans was used to test the effectiveness of frequent application of a chlorhexidine antiplaque solution in reducing the overgrowth. METHODS: Four groups of rats were fed CsA. One group received chlorhexidine mouthwash twice a day, the second group received chlorhexidine mouthwash once a day, the third group received chlorhexidine mouthwash every other day, and the fourth group did not receive chlorhexidine mouthwash all. A fifth negative control group received only mineral oil. Overgrowth was determined by measuring the changes in the gingival probing depth and the keratinized gingival width on molars. A gingival histological examination was performed. RESULTS: Rats treated with mouthwash twice daily exhibited decreased probing depths and gingival widths without statistical significance. Histological examination revealed that CsA treatment caused gingival enlargement, whereas chlorhexidine treatment twice a day diminished the enlargement. CONCLUSION: These findings suggest that chlorhexidine mouthwash used twice daily may reduce the severity of CsA-induced gingival overgrowth. Further research is warranted to determine the optimal dose and treatment regimen.

Effects of systemic Bifidobacterium longum and Lactobacillus rhamnosus probiotics on the ligature-induced periodontitis in rat.

Background/purpose: Probiotics might be beneficial in preventing periodontitis. Effects of Bifidobacterium and Lactobacillus on periodontitis were examined using the ligature-induced rat model. Materials and methods: Thirty-five male Sprague-Dawley rats were divided into control, ligation, Bifidobacterium longum (BL986), Lactobacillus rhamnosus (LRH09), and combination groups. Periodontitis was induced in maxillary second molars. From the day before ligation, phosphate-buffered saline (for control and ligation groups) or probiotics (2 × 109 CFU/g for probiotic groups) were fed daily. On day 8, gingival mRNA expressions for interleukin (IL)-1ß, IL-6, tissue necrosis factor (TNF)-α, IL-10, and NF-κB were determined via qPCR. Micro-computed tomography (µCT) and histomorphometry were employed to examine periodontal destruction. Results: Compared to the ligation group, mRNA of IL-1ß, TNF-α, IL-6, and NF-κB in probiotic groups were significantly decreased, but IL-10 was increased. Besides, the IL-10 was more significant in the combination group than in single-use group. Through µCT, the cementoenamel junction (CEJ)-to-bone distance and trabecular separation in combination group were less than that in ligation group, although the bone volume fraction and trabecular number/thickness showed an increase in three probiotic groups. Histopathologically, the combination group had significantly smaller gingival inflammatory cell-infiltrated area and CEJ-to-epithelium distance than the ligation group and the group with BL986 or LRH09. Additionally, the CEJ-to-bone distance was significantly smaller in the combination group than in the ligation and BL986 groups. Conclusion: Systemic combination of BL986 and LRH09 had a synergistic effect on enhancing IL-10 and ameliorating the induced experimental periodontitis, although the single-use still presented partially alleviative effects.