Aberrant expression of DUSP4 is a specific phenomenon in betel quid-related oral cancer.

Oral cancer due to betel quid chewing habit is very common in South Asian countries. We attempted to detect the presence of a novel gene in epithelial cells stimulated with arecoline, a main component of betel quid. Human gingival epithelial progenitors were cultured and treated with a 3-day alternating regimen with/without 50 µg/ml arecoline for 1 month. DNA microarray and methylation arrays were analyzed to identify the candidate genes. Immunohistochemical staining was performed in the tissue samples. Genome-wide analyses, quantitative reverse transcription PCR and quantitative methylation-specific PCR revealed DUSP4 as the most significant and promising gene. The methylation levels of DUSP4 were significantly higher in the betel quid-related oral squamous cell carcinoma (OSCC) than those in the non-related OSCC and controls (Mann-Whitney U test, p < 0.05). The number of DUSP4 immunopositive cells in betel quid-related OSCC was significantly higher than those from the non-chewing patients and the controls (p < 0.05). Hypermethylation of DUSP4 may be considered as a specific event in betel quid-related oral cancer.

Pharmacotherapy in relieving the symptoms of burning mouth syndrome: A 1-year follow-up study.

OBJECTIVE: Burning mouth syndrome (BMS) is a chronic intraoral burning sensation with no identifiable causes. In this study, we aim to demonstrate the effectiveness of treatment strategy using ethyl loflazepate monotherapy or in combination with milnacipran or amitriptyline. METHOD: A hospital-based, retrospective study was conducted in 86 patients. The patients were divided into remission group and non-remission group. The remission group comprised patients who were satisfied with their pain relief within a year of treatment initiation and did not require any follow-up treatment. The treatment was considered effective if the patient got remission within 1 year or was able to reduce the visual analogue scale (VAS) score to <20, in the absence of remission. RESULTS: The treatment strategy was effective in 76.7% of the patients. Significant reductions (p < .05) in VAS scores from 73.5 ± 14.2 at first visit to 14.7 ± 8.7 at last visit in the remission group, and from 79.7 ± 14.3 at first visit to 33.4 ± 23.7 after 1 year of treatment in the non-remission group were noted. CONCLUSION: The treatment strategy using ethyl loflazepate monotherapy or in combination with milnacipran or amitriptyline can be very effective in reducing pain in BMS patients.

Curcumin inhibits the expression of proinflammatory mediators and MMP-9 in gingival epithelial cells stimulated for a prolonged period with lipopolysaccharides derived from Porphyromonas gingivalis.

Curcumin, a yellow phytochemical found in the rhizomes of Curcuma longa, has various biological effects, including anti-oxidant and anti-inflammatory activities. In the present study, we examined the effect of curcumin on the expression of inflammatory cytokines in human gingival epithelial progenitor cells (HGEPs) stimulated for a prolonged period with lipopolysaccharide (LPS) derived from Porphyromonas gingivalis. The cells were alternately cultured with LPS and/or curcumin every 3 days for 18 days. The expression levels of TNF-α, IL-1ß, IL-6, TIMP-1, and MMP-9 in the HGEPs were evaluated by quantitative real-time polymerase chain reaction. Enzyme-linked immunosorbent assay was used to measure the concentrations of these five proteins in the supernatant and nuclear factor (NF)-κB in the nuclear extracts. Curcumin inhibited the mRNA expression levels of TNF-α, IL-1ß, IL-6, and MMP-9 in HGEPs treated with curcumin over a prolonged period. Similarly, the expression levels of IL-1ß, IL-6, and MMP-9 were decreased in the culture supernatants. NF-κB activity was also inhibited in the cells cultured with curcumin. In conclusion, these findings indicate that curcumin inhibits the expression of inflammatory cytokines and MMP-9 in primary gingival epithelial cells stimulated with P. gingivalis-derived LPS via NF-κB activation.

P. gingivalis Lipopolysaccharide Stimulates the Upregulated Expression of the Pancreatic Cancer-Related Genes Regenerating Islet-Derived 3 A/G in Mouse Pancreas.

Although epidemiological studies have shown a relationship between periodontal disease and pancreatic cancer, the molecular mechanisms involved remain unclear. In this study, the effects of systemic administration of Porphyromonas gingivalis lipopolysaccharide (PG-LPS) on gene expression were comprehensively explored in mouse pancreas that did not demonstrate any signs of inflammation. PG-LPS was prepared in physiological saline and intraperitoneally administered to male mice at a concentration of 5 mg/kg every 3 days for 1 month. After extracting total RNA from the excised mice pancreas, a comprehensive DNA microarray analysis of gene expression was performed. Tissue specimens were also subjected to hematoxylin-eosin staining and immunohistochemistry using anti-regenerating islet-derived 3A and G (Reg3A/G) antibody. ImageJ software was used to quantify the area of Reg3A/G positive cells in pancreatic islets by binarizing image date followed by area extraction. The results were compared using Mann-Whitney U test. Data are presented as mean ± standard deviation (SD) with p < 0.05 considered as significant. Reg3G, a gene related to pancreatic cancer, was one of the 10 genes with the highest levels of expression in the pancreas stimulated with PG-LPS. The comprehensive analysis revealed a 73-fold increase in Reg3G expression level in the PG-LPS group when compared with the control group; in addition, the expression level of Reg3A was increased by 11-fold in the PG-LPS group. Image analysis showed that the ratio of Reg3A/G positive cells was higher in the PG-LPS group than the control. Immunostaining showed the presence of Reg3A/G-positive cells in the alpha-cell equivalent areas around the islets of Langerhans in the PG-LPS group. These results support the notion that periodontal disease may be a risk factor for pancreatic cancer.

Effect of systemic administration of lipopolysaccharides derived from Porphyromonas gingivalis on gene expression in mice kidney.

Although an association between periodontitis and chronic kidney disease (CKD) has been suggested, the mechanism involved remains unclear. Herein, we examined the global gene expression profile in a mouse model that showed no acute inflammation in the kidney following stimulation with lipopolysaccharides (LPS) derived from Porphyromonas gingivalis (PG-LPS). The mice were injected with PG-LPS at a concentration of 5 mg/kg intraperitoneally, every 3 days, for 1 month. Microarray analysis was used to identify 10 genes with the highest expression levels in the kidney stimulated with PG-LPS. Among them, the functions of five genes (Saa3, Ticam2, Reg3b, Ocxt2a, and Xcr1) were known. The upregulation of these genes was confirmed by quantitative polymerase chain reaction assay. Furthermore, we examined whether the expression of these upregulated genes were altered in endothelial cells derived from the kidney, in vitro. The mRNA expression levels of all five genes were significantly higher in the experimental group than in the controls (no LPS stimulation; *p < 0.05). In conclusion, the responses noted in the kidney may have arisen mainly from the endothelial cells. Moreover, upregulation of the expression levels of Saa3, Ticam2, Reg3b, Ocxt2a, and Xcr1 may be associated with the pathogenesis of CKD.

Analysis of DNA methylation of E-cadherin and p16ink4a in oral lichen planus/oral lichenoid lesions.

OBJECTIVES: Epigenetic phenomena are changes in gene expression not involving the DNA sequence. DNA methylation is a major occurrence underlying epigenetic changes in human cells. Although aberrant DNA methylation is well documented in malignant lesions, limited information has been shown on the involvement of DNA methylation in oral lichen planus and oral lichenoid lesions (OLP). The present study aimed to investigate DNA methylation of E-cadherin and p16 in OLP, and compare the findings with those in non-inflamed gingiva (Non), radicular cyst (RC), and oral squamous cell carcinoma (SCC). MATERIALS AND METHODS: Paraffin-embedded surgical biopsy specimens were sliced, DNA was extracted, bisulfite treatment was applied, and methylation-specific polymerase chain reaction was performed. Immunohistochemistry was performed to observe the relative expression patterns of these genes. RESULTS: E-cadherin was hypermethylated in OLP (p < 0.01), SCC (p < 0.01), and RC (p < 0.05), when compared with Non; DNA hypermethylation was confirmed in OLP and SCC when compared to Non and RC. Hypermethylation of p16ink4a was observed only in SCC (p < 0.01). CONCLUSION: DNA methylation levels of E-cadherin and p16ink4a were significantly higher in OLP than in normal tissues, and may be associated with the pathogenesis and progression of the disease.

Alteration of oral flora in betel quid chewers in Sri Lanka.

BACKGROUND: Betel quid chewing is known as a crucial risk factor for oral diseases such as periodontal diseases, oral cancer, and precancerous lesions in Southeast Asian countries. Although abnormal oral bacterial flora may be linked to betel quid related-oral diseases such as oral cancer, precancerous lesions, and periodontal diseases, little information is available on alterations of their oral flora thus far. To identify these alterations, we analyzed the oral flora in betel quid chewers (BQC) and non-chewers (NC) in Sri Lanka. METHODS: Samples obtained from buccal swabs of BQC and NC were analyzed with a next generation sequencer. Data were processed and analyzed using the QIIME software package. Mann-Whitney U test and Permutational multivariate analysis of variance were used for statistical analyses. P values < 0.05 were considered to be statistically significant. RESULTS: In BQC, the proportion of periodontal pathogens including Actinomyces, Tannerella, and Prevotella was higher than that in NC (P < 0.05), while the proportion of cariogenic pathogens including Streptococcus, Lautropia, and Actinobacillus was lower than that in NC (P < 0.05). A statistically significant difference in Shannon index and PD Whole tree was observed between BQC and NC (P < 0.05). PCoA analysis detected different clusters in BQC and NC (P < 0.05). CONCLUSION: The results suggested that betel quid chewing significantly altered oral flora. Adequate oral health care may help prevent BQC from developing bacterial pathogen-related oral diseases.

Association between self-efficacy and loss to follow-up in long-term periodontal treatment.

AIM: To examine whether or not oral health care-specific self-efficacy can predict loss to follow-up for long-term periodontal treatment. METHODS: Our prospective cohort study enrolled 144 patients with chronic periodontitis. Patient self-efficacy was assessed on the initial visit using the self-efficacy scale for self-care (SESS). Participants were then followed for 30 months from the onset of periodontal treatment. The loss to follow-up is the main outcome variable. Multiple logistic regression analysis was conducted to examine the association between self-efficacy for self-care and loss to follow-up for periodontal treatment. Gender, age, number of teeth, probing depth, plaque control record (PCR) value, PCR improvement rate, general self-efficacy scale score, and SESS score were used as the independent variables, and loss to follow-up as a dependent variable. RESULTS: A total of 67 patients were lost to follow-up over the course of the study. Compared with the high-scoring SESS group (60-75), the odds ratio of loss to follow-up for the middle- (54-59) and low-scoring groups (15-53) were 1.05 [95% confidence interval (CI): 0.36-3.07] and 4.56 (95% CI: 1.11-18.74), respectively. CONCLUSION: Assessment of oral health care-specific self-efficacy may be useful in predicting loss to follow-up in long-term periodontal treatment.

Development of the self-efficacy scale for maternal oral care.

PURPOSE: This study's purpose was to develop a task-specific self-efficacy scale for maternal oral care (SESMO) with reliability and validity. METHODS: A draft scale consisting of 36 items was designed and tested on 119 mothers at a dental clinic. Item analysis was performed to improve its accuracy by reducing the number of items. Internal consistency and test and retest stability were investigated. Concurrent validity was tested by examining associations of the SESMO score with the: general self-efficacy scale (GSES) score; number of decayed teeth; and frequency of tooth-brushing for children. Construct validity was examined by comparing the SESMO scores between mothers of children with caries at initial visit (Group 1) and those continuing regular dental checkups (Group 2). RESULTS: The item analysis selected 16 items for the SESMO. Alpha coefficient of the SESMO was 0.82. Significant correlation was observed between tests and retests (r=0.74). There were significant associations between the SESMO score and GSES score (r=0.39); number of decayed teeth (r=-0.33); and frequency of brushing children's teeth (r=0.66). Group 2 had a significantly higher SESMO score than Group 1 (P<.001). CONCLUSIONS: The SESMO showed high reliability and validity. This scale might endure with research applications in pediatric dental practice.

DNA hypermethylation of sirtuin 1 (SIRT1) caused by betel quid chewing-a possible predictive biomarker for malignant transformation.

BACKGROUND: DNA hypermethylation of tumor suppressor genes is observed in precancerous lesions and oral cancer of individuals with the habits of betel quid (BQ) chewing. SIRT1 has been identified as playing a role in the maintenance of epithelial integrity, and its alteration is often related to carcinogenesis. However, the methylation and transcription status of SIRT1 in patients with BQ chewing-related oral cancer has not been investigated. We examined the methylation status of SIRT1 in paraffin-embedded tissue samples of oral squamous cell carcinoma (OSCC) obtained from BQ chewing and non-chewing patients and in tissue samples from healthy control subjects. In addition, we examined whether the hypermethylation of SIRT1 followed by its transcriptional downregulation in the human gingival epithelial cells could be caused by arecoline, a major component of BQ. Furthermore, we investigated the methylation status of SIRT1 in smear samples of macroscopically healthy buccal mucosa from subjects with a habit of BQ chewing. RESULTS: SIRT1 was significantly hypermethylated in tissue samples of OSCC from BQ chewers and non-chewers than in oral mucosa from healthy control subjects. Results also showed that the hypermethylation level of SIRT1 was significantly higher in OSCC of patients with BQ chewing habits than in those of non-chewing habits (p < 0.05). Our in vitro model showed that hypermethylation is followed by downregulation of the transcriptional level of SIRT1 (p < 0.05). The methylation levels of SIRT1 in the smear samples obtained from BQ chewing individuals were significantly higher than those in the samples obtained from individuals that did not chew BQ. The duration of BQ chewing habits was correlated positively to the frequency of SIRT1 hypermethylation (p < 0.05). CONCLUSIONS: Our results suggest that DNA hypermethylation of SIRT1 is involved in the occurrence of oral cancer in BQ chewing patients and that hypermethylation in the oral mucosa of BQ chewers could be a predictive marker for the occurrence of malignant transformation. This is the first report that showed DNA hypermethylation in clinically healthy oral epithelium of BQ chewers. Our study shows evidence that DNA hypermethylation may be an early event of oral carcinogenesis prior to observable clinical changes.

Cognitive behavioral therapy for psychosomatic problems in dental settings.

Cognitive behavioral therapy (CBT) has been applied for various problems, including psychiatric diseases such as depression and anxiety, and for physical symptoms such as pain. It has also been applied for dental problems. Although the effect of CBTs on temporomandibular disorders and dental anxiety are well documented, its effectiveness on other types of oral symptoms remain unclear. Little information comparing the different types of CBTs in the dental setting is currently available. Because dental professionals are often expected to conduct CBTs in the dental setting, it is important to develop proper training programs for dental professionals. In this review article, we demonstrate and discuss the application of CBTs for psychosomatic problems, including temporomandibular disorders, dental anxiety, burning mouth syndrome, and other oral complaints in dental settings.

Upregulated expression of MMP-9 in gingival epithelial cells induced by prolonged stimulation with arecoline.

Betel quid chewing is implicated in the high prevalence of oral cancer in Southeast Asian countries. One of the major components of betel quid is arecoline. In the present study, in order to characterize the association between chronic arecoline stimulation and carcinogenesis the expression level of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 mRNA in human gingival epithelial progenitor cells (HGEPs) stimulated with arecoline was assessed. The HGEPs were alternated between 3 days of incubation with arecoline (50 µg/ml), and 3 days without arecoline, for up to 30 days. The expression levels of the MMPs and TIMPs in the cells stimulated with arecoline were evaluated by reverse transcription-quantitative polymerase chain reaction at 18 and 30 days. The expression of MMP-9 mRNA in the experimental group was significantly increased compared with in the control group (P<0.01). No significant differences in the expression of MMP-2, TIMP-1 or TIMP-2 mRNA were observed between the experimental and control groups. Using an MMP-9 activity assay, the levels of MMP-9 activity in the experimental group were demonstrated to be significantly higher than in the control group (P<0.05). To investigate associated cellular signaling pathways, PDTC [a nuclear factor (NF)-κB/inhibitor of NF-κB (IκB) inhibitor], PD98059 [a mitogen-activated protein kinase kinase (MAPKK)1 and MAPKK2 inhibitor], SB203580 (a p38 MAPK inhibitor) and 5,15-DPP [a signal transduction and activator of transcription (STAT) 3 inhibitor] were used. All inhibitors decreased the extent of MMP-9 upregulation induced by stimulation with arecoline. Based on the data, it is hypothesized that MMP-9 activity may be involved in the pathological alterations of oral epithelium induced by betel quid chewing, and that the NF-κB/IκB, MAPK, p38 MAPK and STAT3 signaling pathways may be involved in the production of MMP-9 induced by betel quid chewing.

Osteoprotegerin protects endothelial cells against apoptotic cell death induced by Porphyromonas gingivalis cysteine proteinases.

Osteoprotegerin (OPG) is a key regulator of osteoclastogenesis during the progression of periodontitis. Recent reports suggest that osteoprotegerin may also prevent arterial calcification and contribute to endothelial cell survival. To determine whether the vascular functions of osteoprotegerin are involved in periodontitis, we examined whether osteoprotegerin contributed to the survival of endothelial cells damaged by Porphyromonas gingivalis cysteine proteinases (gingipains). Gingipain proteinases cleave a broad range of host proteins, and are important virulence factors of P. gingivalis, a major causative bacterium of adult periodontitis. Human microvascular endothelial cells (HMVEC) were exposed to activated gingipain extracts from P. gingivalis 381, with and without pretreatment with osteoprotegerin. Cell viability was quantified by the tetrazolium (WST-8) reduction assay, and apoptosis was examined using Hoechst 33342 nuclear staining. After 16 h of treatment with activated gingipain extracts, HMVEC showed near-complete detachment from the tissue culture dish, and apoptosis was evident by 24 h. Pretreatment of HMVEC with osteoprotegerin reduced the extent of both cellular detachment and apoptotic cell death. Our results indicated that osteoprotegerin pretreatment protected HMVEC against detachment and apoptotic cell death induced by gingipain-active bacterial cell extracts. These results also suggest that osteoprotegerin may function as a survival factor for endothelial cells during periodontitis.

The effect of cognitive appraisal for stressors on the oral health-related QOL of dry mouth patients.

BACKGROUND: Dry mouth is very common symptom, and psychological factors have an influence on this symptom. Although the influence of emotional factor related to patients with oral dryness has been examined in previous studies, the cognitive factors have not been examined thus far. OBJECTIVE: The purpose of this study was to examine the influence of cognitive factors on patients with oral dryness. METHODS: The participants were 106 patients complaining of oral dryness. They were required to complete a questionnaire measuring subjective oral dryness, oral-related QOL, cognition for stressors, and mood state. RESULTS: Correlational analyses revealed that OHIP-14 is significantly related to oral dryness, appraisal for effect, appraisal for threat, and commitment. These correlations were maintained even after controlling for the influence of depression and anxiety. Using oral dryness, appraisal for effect, appraisal for threat, and commitment, cluster analysis was done and three clusters (cluster-1, severe oral dryness; cluster-2, positive cognitive style: cluster-3, negative cognitive style) were extracted. The results of ANOVA showed that the group with severe oral dryness (cluster-1) had a significantly higher score on OHIP-14 than the other two groups. There was no significant difference between the groups with positive (cluster-2) and negative (cluster-3) cognitive style. CONCLUSION: Although the group of patients with positive cognitive style complained of more severe oral dryness than the group with negative cognitive style, no significant difference was observed between these two groups in OHIP-14. These results indicate that cognitive factors would be a useful therapeutic target for the improvement of the oral-related QOL of patients with oral dryness.

Current evidence on atypical odontalgia: diagnosis and clinical management.

Patients with atypical odontalgia (AO) complain of medically unexplained toothache. No evidence-based diagnostic criteria or treatment guidelines are yet available. The present paper addresses seven clinical questions about AO based on current knowledge in the literature and discusses diagnostic criteria and guidelines for treatment and management. The questions are (i) What is the prevalence of AO in the community? (ii) What psychological problems are experienced by patients with AO? (iii) Are there any comorbidities of AO? (iv) Is local anesthesia effective for the relief of pain in AO? (v) Are there any characteristic symptoms of AO other than spontaneous pain? (vi) Are antidepressants effective for treatment of AO? (vii) Are anticonvulsants effective for treatment of AO? Our literature search provided answers for these questions; however, there is insufficient evidence-based data to establish guidelines for the diagnosis and treatment of AO. Overall, some diagnostic criteria for neuropathic pain and persistent dentoalveolar pain disorder may be applied to AO patients. The patient's psychogenic background should always be considered in the treatment and/or management of AO. The clinicians may need to treat AO patients using Patient-Oriented Evidence that Matters approach.

Development of the outcome expectancy scale for self-care among periodontal disease patients.

RATIONALE: The theory of self-efficacy states that specific efficacy expectations affect behaviour. Two types of efficacy expectations are described within the theory. Self-efficacy expectations are the beliefs in the capacity to perform a specific behaviour. Outcome expectations are the beliefs that carrying out a specific behaviour will lead to a desired outcome. OBJECTIVE: To develop and examine the reliability and validity of an outcome expectancy scale for self-care (OESS) among periodontal disease patients. METHODS: A 34-item scale was tested on 101 patients at a dental clinic. Accuracy was improved by item analysis, and internal consistency and test-retest stability were investigated. Concurrent validity was tested by examining associations of the OESS score with the self-efficacy scale for self-care (SESS) score and plaque index score. Construct validity was examined by comparing OESS scores between periodontal patients at initial visit (group 1) and those continuing maintenance care (group 2). RESULTS: Item analysis identified 13 items for the OESS. Factor analysis extracted three factors: social-, oral- and self-evaluative outcome expectancy. Cronbach's alpha coefficient for the OESS was 0.90. A significant association was observed between test and retest scores, and between the OESS and SESS and plaque index scores. Further, group 2 had a significantly higher mean OESS score than group 1. CONCLUSION: We developed a 13-item OESS with high reliability and validity which may be used to assess outcome expectancy for self-care. A patient's psychological condition with regard to behaviour and affective status can be accurately evaluated using the OESS with SESS.

Anti-cell-associated glucosyltransferase immunoglobulin Y suppression of salivary mutans streptococci in healthy young adults.

BACKGROUND: The authors evaluated the suppressive effects of lozenges containing egg yolk antibodies (that is, immunoglobulin Y [IgY]) against Streptococcus mutans cell-associated glucosyltransferase (CA-gtf) on oral colonization by mutans streptococci (MS) in healthy young adults. METHODS: In a five-day double-masked placebo-controlled trial, young adult participants self-administered lozenges containing anti-CA-gtf IgY (Ovalgen DC, GHEN, Gifu-City, Japan) or a placebo at prescribed times each day. On the basis of bacterial colony counts of saliva cultures, the authors analyzed the pretrial and posttrial differences in levels of MS and total anaerobic bacteria among participants in the treatment (anti-CA-gtf IgY) and placebo groups and a control group. RESULTS: Salivary MS scores in participants in the treatment group decreased significantly (P < .001), and the mean anaerobic bacterial count in the treatment group was not statistically different before and after the trial. In the placebo and control groups, posttrial changes in median MS scores and total salivary anaerobic bacterial counts were not statistically significant. CONCLUSIONS: The results of the study show that lozenges containing anti-CA-gtf IgY can suppress oral colonization by MS in healthy young adults. CLINICAL IMPLICATIONS: Lozenges containing anti-CA-gtf IgY may help reduce dental caries risk in humans.

Relationship between salivary histatin 5 levels and Candida CFU counts in healthy elderly.

OBJECTIVES: Few epidemiological studies have confirmed the antifungal activity of histatin 5 in saliva against Candida species. The purpose of this study was to examine the relationship between concentrations of histatin 5 and the number of cultivable Candida in saliva samples from elderly. METHODS: Whole saliva samples were obtained from 124 elderly people, 65 years or older, living in a rural community. The concentrations of histatin 5 in saliva samples were determined by the enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody. Total colony-forming units (CFUs) were counted on a selective medium for Candida. Multiple linear regression analysis was performed to determine the independent contribution of explanatory variables to Candida CFUs using age, sex, histatin 5 concentration and type of denture prosthesis as independent variables. RESULTS: Saliva samples from 104 subjects (84%) were candidal colony-positive. The youngest group (65-69 years old) showed significantly smaller Candida CFU counts than those in the older group. The mean Candida CFU count of denture wearers was significantly higher than that of non-denture wearers. Significantly negative associations were found between Candida CFU counts and histatin 5 level in the oldest group (p < 0.05) and in the full-denture wearers (p < 0.01). Multiple linear regression analysis revealed that Candida CFU counts were mostly associated with type of dentures, followed by histatin 5 concentration. CONCLUSION: Possible activity of histatin 5 against Candida in whole saliva of elderly people was epidemiologically confirmed. The area covered by the prostheses was a strong factor associated with the Candida CFU count.

NF-kappaB-dependent induction of osteoprotegerin by Porphyromonas gingivalis in endothelial cells.

Porphyromonas gingivalis is a major etiological pathogen of adult periodontitis characterized by alveolar bone resorption. Vascular endothelial cells supply many inflammatory cytokines into periodontal tissue. However, whether the cells contribute to bone metabolism in periodontitis remains unknown. In this study, we investigated the effect of P. gingivalis on osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) production, both of which are key regulators of bone metabolism, in human microvascular endothelial cells (HMVECs). We showed that P. gingivalis upregulated expression of OPG but not RANKL mRNA in HMVEC. P. gingivalis induced NF-kappaB activation, and the induction of OPG in HMVEC by the pathogen was blocked by the inhibitors of NF-kappaB. In addition, incubation of OPG with P. gingivalis supernatant resulted in loss of the protein. These results indicate that P. gingivalis-stimulated HMVEC secrete OPG via a NF-kappaB-dependent pathway, while the OPG is partly degraded by the bacteria. Thus, microvascular endothelial cells can act as a source of OPG and thereby may play an important role in regulating bone metabolism in periodontitis.