Search tips
Search criteria

Results 1-25 (97)

Clipboard (0)

Select a Filter Below

Year of Publication
more »
Document Types
1.  Birth Weight of Infants of Mothers With Aggressive Periodontitis 
Journal of periodontology  2011;83(3):279-286.
It was hypothesized that if periodontal infections predispose low birth weights and premature birth, then such outcomes should be apparent when the mother has aggressive periodontitis (AgP).
Birth weight data were collected by questionnaire from females with AgP, their periodontally healthy siblings, and unrelated periodontally healthy women. Both prospective and retrospective birth outcome data were used. Because many of the periodontal evaluations were performed after the births, there were incomplete data regarding most of the risk factors for low birth weight. We determined associations between mothers’ periodontal diagnoses and clinical variables and the reported birth weights.
There were no significant differences in mean birth weights of babies born to control subjects or AgP patients. This was true whether all the births were considered or only those reported <1 or 2 years before periodontal examination. For periodontally healthy controls, 13.2% of babies born to siblings of AgP patients and 12.8% of babies born to unrelated mothers weighed <2,500 g, whereas 9.9% of those born to mothers with generalized AgP and 10.3% of those born to mothers with localized AgP weighed <2,500 g.
Because of the relative rarity of AgP in the population, and attendant difficulties in performing a prospective study of its association with pregnancy outcomes, we used a compromised approach using prospective data as well as weaker retrospective data assuming that disease onset was likely before the births. Our results, within the limitations of this approach, indicate no evidence that AgP in the mother predisposes low birth weights. AgP has many unique biologic characteristics that differentiate it from chronic forms of periodontal disease, and the possible lack of its association with birth weight may be another such characteristic.
PMCID: PMC4063275  PMID: 21819247
Aggressive periodontitis; infant, low birth weight; pregnancy; preterm birth
2.  Comparison of microbial changes in early re-developing biofilms on natural teeth and dentures 
Journal of periodontology  2012;83(9):1139-1148.
Background and objective
Surfaces and fluids can affect oral bacterial colonization. The aim of this study was to compare re-developing biofilms on natural teeth and dentures.
Supragingival plaque samples were taken from 55 dentate subjects and the denture teeth of 62 edentulous subjects before and after professional cleaning. Also, samples from 7 “teeth” in randomly selected quadrants were collected after 1, 2, 4 and 7 days of no oral hygiene. Samples were analyzed using checkerboard DNA-DNA hybridization. Counts and proportions of 41 bacterial taxa were determined at each time point and significant differences were sought using the Mann-Whitney test. Ecological succession was determined using a modified moving window analysis.
Mean total DNA probe counts were similar pre-cleaning but were higher in dentate subjects at all post-cleaning visits (p<0.01). Pre-cleaning edentate biofilms had higher counts and proportions of Streptococcus mitis, Streptococcus oralis and Streptococcus mutans, whereas dentate subjects had higher proportions of Tannerella forsythia, Selenomonas noxia and Neisseria mucosa. By 2 days, mean counts of all taxa were higher in natural teeth and most remained higher at 7 days (p<0.01). Succession was more rapid and complex in dentate subjects. Both groups demonstrated increased proportions of S. mitis and S. oralis by 1 day. N. mucosa, Veillonella parvula and Eikenella corrodens increased in both groups but later in edentate samples.
“Mature” natural and denture teeth biofilms have similar total numbers of bacteria but different species proportions. Post-cleaning biofilm re-development is more rapid and more complex on natural than denture teeth.
PMCID: PMC4041159  PMID: 22443543
microbiota; biofilms; supragingival; dental plaque; tooth; dentures
3.  Epigenetic Regulation of TNFA Expression in Periodontal Disease 
Journal of periodontology  2013;84(11):1606-1616.
Tumor necrosis factor-alpha (TNF-α) plays a central role in the molecular pathogenesis of periodontal disease. However, the epigenetic regulation attributable to microbial and inflammatory signals at the biofilm gingival interface are poorly understood. In this study, we investigated the DNA methylation alteration within the TNFA promoter in human gingival biopsies from different stages of periodontal disease, and explored the regulatory mechanism of TNFA transcription by DNA methylation.
Gingival biopsies were harvested from 17 chronic periodontitis patients and 18 subjects with periodontal health. Another 11 subjects participated in an experimentally induced gingivitis study, and gingival biopsies were collected at the baseline, induction, and resolution phase. To confirm that TNFA promoter methylation modulated TNFA transcription we treated THP.1 cells with a DNA methyltransferase inhibitor, 5-aza-2-deoxycytidine and used a RAW 294.7 cell line transfected with a TNFA promoter-specific luciferase reporter system with or without methlyaiton,
In gingival biopsies from subjects with severe chronic periodontitis two individual CpG sites within the TNFA promoter (at -163bp and -161bp) displayed increased methylation in periodontitis samples as compared to gingival health (16.1±5.1% vs. 11.0±4.6%, p=0.02, 19.8±4.1% vs. 15.4±3.6%, p=0.04, respectively). The methylation level at -163bp was inversely associated with the transcription level of TNFA (p=0.018). However, no significant difference in the TNFA promoter methylation pattern was observed in samples biopsied during the induction or resolution phase of experimentally induced gingivitis, which represented a reversible periodontal lesion. THP.1 cells treated with 5-aza-2-deoxycytidine demonstrated a time-dependent increase in TNFA messenger level. We also found that the luciferase activity decreased 2.6 fold in a construct containing an in vitro methylated TNFA promoter as compared to the unmethylated insert (p=0.03).
Although the biopsy samples represented a mixed cell population, the change in promoter methylation status in chronic periodontal disease suggested that DNA methylation may be an important regulatory mechanism in controlling TNFA transcriptional expression in disease.
PMCID: PMC3986590  PMID: 23368949
4.  Periodontal Disease as a Risk Factor for Bisphosphonate-Related Osteonecrosis of the Jaw 
Journal of periodontology  2013;85(2):226-233.
Previous case reports and animal studies suggest periodontitis is associated with bisphosphonate-related osteonecrosis of the jaw (BRONJ). We conducted a case-control study to evaluate the association between clinical and radiographic measures of periodontal disease and BRONJ.
25 BRONJ patients were matched with 48 controls. Trained examiners measured probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP) on all teeth except third molars, and gingival and plaque indices on six index teeth. Alveolar bone height was measured from orthopantomograms. Most BRONJ cases were using antibiotics (48%) or a chlorhexidine mouthrinse (84%) at enrollment. Adjusted comparisons of cases vs. controls used multiple linear regression.
The average number of BP infusions was significantly higher in BRONJ cases compared to controls (38.4 vs 18.8, p=0.0001). In unadjusted analyses, BRONJ cases had more missing teeth (7.8 vs 3.1, p=0.002) and high average CAL (2.18 vs 1.56 mm, p=0.047) and percent of sites with CAL ≥3 mm (39.0 vs 23.3, p=0.039) than controls. Also, BRONJ cases had lower average bone height (as a fraction of tooth length, 0.59 vs 0.62, p=0.004) and more teeth with bone height under half of tooth length (20% vs 6%, p=0.001). These differences remained significant after adjusting for age, sex, smoking, and number of bisphosphonate infusions.
BRONJ patients have fewer teeth, greater CAL, and less alveolar bone support compared to controls after adjusting for number of bisphosphonate infusions. Group differences in antibiotics and chlorhexidine rinse usage may have masked differences in the other clinical measures.
PMCID: PMC3972496  PMID: 23786404
Bisphosphonates; Periodontitis; Periodontal Disease; Alveolar Bone Loss; Osteonecrosis; Bisphosphonate-related osteonecrosis of the jaw
5.  Impact of Periodontal Therapy on the Subgingival Microbiota of Severe Periodontitis: Comparison between Good Responders and “Refractory” Subjects by the Human Oral Microbe Identification Microarray (HOMIM) 
Journal of periodontology  2012;83(10):1279-1287.
This study compared the changes on the subgingival microbiota of subjects with “refractory” periodontitis (RP) or treatable periodontitis (GR) before and after periodontal therapy by using the Human Oral Microbe Identification Microarray (HOMIM).
Individuals with chronic periodontitis were classified as RP (n=17) based on mean attachment loss (AL) and/or >3 sites with AL ≥2.5 mm after scaling and root planing, surgery and systemically administered amoxicillin and metronidazole or as GR (n=30) based on mean attachment gain and no sites with AL ≥2.5 mm after treatment. Subgingival plaque samples were taken at baseline and 15 months after treatment and analyzed for the presence of 300 species by HOMIM analysis. Significant differences in taxa before and after therapy were sought using the Wilcoxon test.
The majority of species evaluated decreased in prevalence in both groups after treatment; however, only a small subset of organisms was significantly affected. Species that increased or persisted in high frequency in RP but were significantly reduced in GR included Bacteroidetes sp., Porphyromonas endodontalis, Porphyromonas gingivalis, Prevotella spp., Tannerella forsythia, Dialister spp., Selenomonas spp., Catonella morbi, Eubacterium spp., Filifactor alocis, Parvimonas micra, Peptostreptococcus sp. OT113, Fusobacterium sp. OT203, Pseudoramibacter alactolyticus, Streptococcus intermedius or Streptococcus constellatus and Shuttlesworthia satelles. In contrast, Capnocytophaga sputigena, Cardiobacterium hominis, Gemella haemolysans, Haemophilus parainfluenzae, Kingella oralis, Lautropia mirabilis, Neisseria elongata, Rothia dentocariosa, Streptococcus australis and Veillonella spp. were more associated with therapeutic success.
Persistence of putative and novel periodontal pathogens, as well as low prevalence of beneficial species was associated with chronic “refractory” periodontitis.
PMCID: PMC3971922  PMID: 22324467
Refractory Periodontal Disease; Non-surgical periodontal therapy; antimicrobials; DNA microarrays; Microbiology
6.  Blocking Pro-Inflammatory Cytokine Release Modulates Peripheral Blood Mononuclear Cell Response to Porphyromonas Gingivalis 
Journal of periodontology  2012;84(9):1337-1345.
Chronic periodontitis is an inflammatory disease in which cytokines play a major role in the progression of disease. Anti-inflammatory cytokines (IL-4 and IL-10) were reported to be absent or reduced in diseased periodontal tissues, suggesting an imbalance between the pro- and anti-inflammatory mediators. We have tested the hypothesis that there is cellular cross-talk mediated by pro- and anti-inflammatory cytokines and that blocking pro-inflammatory cytokine (TNF-α and IL-1) production will enhance anti-inflammatory cytokine (IL-4 and IL-10) production from peripheral blood mononuclear cells (PBMC) in response to P. gingivalis.
PBMC were isolated from individuals diagnosed with chronic periodontitis or healthy individuals and cultured for 24 hours. Concanavalin-A (ConA) was used as an activator of lymphocyte function. Live and heat-killed P .gingivalis or lipopolysaccharide from P. gingivalis was used as the bacterial stimulants. TNF-α and IL-1 production was neutralized by specific antibodies against TNF-α and IL-1α or β. Culture supernatants were evaluated by ELISA for TNF-α, IL-1β, IL-4, and IL-10 production.
Live P. gingivalis did not result in any significant IL-10 or IL-4 release while heat-killed P. gingivalis led to a significant increase in IL-10 levels compared to unstimulated or live P. gingivalis-stimulated cells from both healthy and periodontitis individuals. Overall, PBMC from patients with chronic periodontitis produced significantly lower IL-10 in response to ConA and P. gingivalis suggesting chronic suppression of the anti-inflammatory cytokine production. Blocking the pro-inflammatory cytokine response did not result in any substantial change in IL-10 or IL-4 response to live P. gingivalis. Blocking the pro-inflammatory cytokine response restored IL-10 production by cells from chronic periodontitis in response to P. gingivalis LPS.
These findings suggest that PBMC from patients with chronic periodontitis have suppressed anti-inflammatory cytokine production that can, in part, be restored by neutralizing pro-inflammatory cytokines. Monocytes are an important source of IL-10 production and monocyte-derived IL-10 might play a regulatory role in the pathogenesis of chronic periodontitis.
PMCID: PMC3935330  PMID: 23173823
IL-4; IL-10; monocytes; Porphyromonas gingivalis; Periodontitis
7.  Guided bone regeneration (GBR) utilizing injectable Vascular Endothelial Growth Factor (VEGF) delivery gel 
Journal of periodontology  2012;84(2):230-238.
Vascularization underlies the success of guided bone regeneration (GBR) procedures. This study evaluated the regenerative potential of GBR in combination with Vascular Endothelial Growth Factor (VEGF) delivery, via an injectable hydrogel system.
Critical-sized defects were created in rat calvariae and GBR procedures were performed with a collagen membrane either alone (control), plus bolus delivery of VEGF, or plus application of VEGF releasing hydrogels (VEGF - Alg). Four and eight weeks following treatment, defect sites were evaluated with microcomputed tomographic and histomorphometric analyses for blood vessel and bone formation.
At four weeks, relative to the control condition, the bolus addition of VEGF did not affect blood vessel density within the defect site; yet, the application of the VEGF+ Alg significantly (p< 0.05) increased blood vessel density. Though there was no difference in bone regeneration at four weeks, at eight weeks, there was a significant (p < 0.05) increase in bone regeneration in the VEGF + Alg treated defects.
These data demonstrated that the application of VEGF + Alg enhanced early angiogenesis while at a later timepoint, it enhanced bone regeneration. Controlled delivery approaches of angiogenic growth factors used adjunctively with GBR may be a promising strategy for enhancing outcomes of GBR.
PMCID: PMC3669541  PMID: 22668339
regenerative medicine; bioengineering; growth factors; hydrogel; bone; angiogenesis
8.  Modulation of phosphate/pyrophosphate metabolism to regenerate the periodontium. A novel in vivo approach 
Journal of periodontology  2011;82(12):10.1902/jop.2011.110103.
The developing periodontium is sensitive to local levels of phosphate (Pi) and pyrophosphate (PPi), as demonstrated by cementum phenotypes resulting from loss of function of protein regulators of Pi/PPi homeostasis. The progressive ankylosis protein (ANK) regulates transport of PPi, and Ank knock-out (KO) mice feature rapidly forming and thick cementum. We hypothesized that, besides affecting cementum formation, decreased extracellular PPi levels in Ank KO mice would also impact cementum regeneration.
Periodontal fenestration defects (2mm/1mm/0.5mm) were created on the buccal aspects of mandibular molars in Ank KO and wild-type (WT) mice. Mandibles were harvested at 15 and 30 days post-surgery for histology, histomorphometry, evaluation of in vivo fluorochrome labeling, and immunohistochemistry(IHC) for proteins including bone sialoprotein (BSP), osteopontin (OPN), dentin matrix protein 1 (DMP1), and ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1).
A greater amount of new cementum was observed for Ank KO mice at 15 and 30 days post-surgery (p<0.05), that was confirmed by fluorochrome labeling showing a higher new cementum appositional activity in the defect areas in Ank KO vs. controls. At days 15 and 30 during healing, regenerating cementum and associated cells in Ank KO recapitulated expression patterns mapped during development, including limited BSP and positive OPN and DMP1 in the cementum matrix, as well as elevated NPP1 in cementoblasts.
Within the limits of the study, these findings suggest that reduced local levels of PPi can promote increased cementum regeneration. Therefore, local modulation of Pi/PPi may be a potential therapeutic approach for achieving improved cementum regeneration.
PMCID: PMC3884815  PMID: 21488756
cementum; periodontal regeneration; ankylosis protein; mouse; pyrophosphates; inorganic phosphates
9.  Correction of hypophosphatasia (HPP) associated mineralization deficiencies in vitro by phosphate/pyrophosphate modulation in periodontal ligament cells 
Journal of periodontology  2011;83(5):10.1902/jop.2011.110310.
Mutations in the Alpl gene in hypophosphatasia (HPP) reduce the function of tissue nonspecific alkaline phosphatase (TNAP), resulting in increased pyrophosphate (PPi) and a severe deficiency in acellular cementum. We hypothesized that exogenous phosphate (Pi) would rescue the in vitro mineralization capacity of periodontal ligament (PDL) cells harvested from HPP-diagnosed subjects, by correcting Pi/PPi ratio and modulating expression of genes involved with Pi/PPi metabolism.
Ex vivo and in vitro analyses were employed to identify mechanisms involved in HPP-associated PDL/tooth root deficiencies. Constitutive expression of PPi-associated genes was contrasted in PDL versus pulp tissues obtained from healthy subjects. Primary PDL cell cultures from HPP subjects (monozygotic twin males) were established to assay alkaline phosphatase activity (ALP), in vitro mineralization, and gene expression. Exogenous Pi was provided to correct Pi/PPi ratio.
PDL tissues obtained from healthy individuals featured higher basal expression of key PPi regulators, genes Alpl, progressive ankylosis protein (Ankh) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1), versus paired pulp tissues. A novel Alpl mutation was identified in the twin HPP subjects enrolled in this study. Compared to controls, HPP-PDL cells exhibited significantly reduced ALP and mineralizing capacity, which were rescued by addition of 1mM Pi. Dysregulated expression of PPi regulatory genes Alpl, Ankh, and Enpp1 was also corrected by adding Pi, though other matrix markers evaluated in our study remained down-regulated.
These findings underscore the importance of controlling Pi/PPi ratio toward development of a functional periodontal apparatus, and support Pi/PPi imbalance as the etiology of HPP-associated cementum defects.
PMCID: PMC3871996  PMID: 22014174
hypophosphatasia; cementum; periodontal ligament; phosphate; pyrophosphate
10.  Relationships Among IL-6, TNF-α, Adipokines, Vitamin D and Chronic Periodontitis 
Journal of periodontology  2011;83(9):1183-1191.
to explore relationships among serum adipokines, vitamin D, clinical and microbial parameters of chronic periodontitis before and after treatment.
weight, height and smoking status were recorded for 56 patients with chronic periodontitis. Plaque, gingivitis, bleeding on probing (BOP), suppuration, pocket depth (PD) and attachment level (AL) were measured at all teeth present. Subgingival biofilm samples from each tooth were analyzed for levels of 40 bacterial species using checkerboard DNA-DNA hybridization. Serum levels of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), adiponectin, leptin, resistin and vitamin D were measured at baseline. Sample collection was then performed in a subset of the population 6 months post-therapy (n=17). Serum samples were analyzed using ELISA and immunoassays. Differences in clinical, microbial and serum factors among groups were sought using the Mann-Whitney test. Correlations among factors were evaluated using regression analysis. Effects of therapy were sought using the Wilcoxon signed ranks test
There were positive correlations between adiponectin/vitamin D and between IL-6/leptin; negative correlations between IL-6/vitamin D, and leptin/vitamin D, but no associations between serum analytes and clinical or microbial parameters. Gender and BMI were associated with levels of adipokines. Periodontal therapy improved clinical and microbiological parameters, but did not influence the levels of serum analytes.
Adipokines and IL-6 levels were affected by gender and BMI. Serum analytes were not influenced by periodontal therapy.
PMCID: PMC3678944  PMID: 22181684
adipokines; cytokines; calcitriol; periodontitis; subgingival scaling; biofilm; microbiota
11.  Plasma 25-hydroxyvitamin D concentrations and periodontal disease in postmenopausal women 
Journal of periodontology  2012;84(9):1243-1256.
Vitamin D has anti-inflammatory and anti-microbial properties that, together with its influence on bone health, may confer periodontal benefit.
We investigated cross-sectional associations (1997–2000) between plasma 25-hydroxyvitamin D concentrations [25(OH)D] and periodontal measure among 920 postmenopausal women. Chronic measures of disease were defined based on: 1) alveolar crestal height (ACH) measures from intraoral radiographs and tooth loss, and the 2) Center for Disease Control and Prevention (CDC)/American Academy of Periodontology (AAP) criteria using measures of clinical attachment level (CAL) and probing pocket depth (PD). Acute oral inflammation was assessed by the % of gingival sites that bled upon assessment with a probe. Logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CIs) for periodontal disease among participants with adequate ([25(OH)D]≥50 nmol/L) compared to deficient/inadequate ([25(OH)D]<50 nmol/L) vitamin D status adjusted for age, dental visit frequency, and body mass index.
No association was observed between vitamin D status and periodontal disease defined by ACH and tooth loss (adjusted OR=0.96, 95% CI: 0.68–1.35). In contrast, women with adequate compared to deficient/inadequate vitamin D status had a 33% lower odds (95% CI: 5%–53%) of periodontal disease defined using the CDC/AAP definition and a 42% lower odds (95% CI: 21%-58%) of having ≥50% of gingival sites that bled.
Vitamin D status was inversely associated with gingival bleeding, an acute measure of oral health and inflammation and inversely associated with clinical categories of chronic periodontal disease that incorporated PD, an indicator of oral inflammation. However, vitamin D was not associated with chronic periodontal disease based on measures of ACH in combination with tooth loss.
PMCID: PMC3745794  PMID: 23259413
vitamin D; 25-hydroxyvitamin D; periodontal diseases; postmenopausal period; epidemiology; women
12.  Cross-sectional Study of Vitamin D and Calcium Supplementation Effects on Chronic Periodontitis 
Journal of periodontology  2009;80(9):1433-1439.
Low dietary intakes of vitamin D and calcium hasten bone loss and osteoporosis. Because vitamin D metabolites may also alter the inflammatory response and have anti-microbial effects, we studied whether use of vitamin D and calcium supplements affects periodontal disease status.
A cohort of 51 subjects receiving periodontal maintenance therapy was recruited from 2 dental clinics. Of these, 23 were taking vitamin D (≥400 international units/day) and calcium (≥1000mg/day) supplementation, and 28 were not taking such supplementation. All subjects had ≥2 interproximal sites with ≥3 mm clinical attachment loss. Daily calcium and vitamin D intakes (from food and supplements) were estimated by nutritional analysis. The following clinical parameters of periodontal disease were recorded for the mandibular posterior teeth: gingival index, probing depth, cementoenamel junction-gingival margin distance (attachment loss), bleeding upon probing, and furcation involvement. Posterior photostimulable-phosphor bitewing radiographs were taken to determine cementoenamel-junction-alveolar-crest distances (alveolar crest height loss). Data were analyzed with a repeated-measures, multivariate analysis of variance.
Relative to subjects who did not take vitamin D and calcium supplementation, supplement takers had shallower probing depths, fewer bleeding sites, lower gingival index values, fewer furcation involvements, less attachment loss and less alveolar crest height loss. The repeated-measures analysis indicated that collectively these differences for clinical parameters were borderline significant (P=0.08).
In these subjects receiving periodontal maintenance therapy, there was a trend for better periodontal health with intake of vitamin D and calcium supplementation. More expanded longitudinal studies are required to determine the potential of this relationship.
PMCID: PMC3706188  PMID: 19722793
vitamin D; calcium; chronic periodontitis; alveolar bone
13.  Depot Medroxyprogesterone Acetate Use and Periodontal Health in United States Women Ages 15-44 
Journal of periodontology  2012;83(8):1008-1017.
One sentence summary
Women who indicate DMPA use have a significantly increased risk of prevalence of periodontal conditions as compared to women who have never used DMPA.
PMCID: PMC3704052  PMID: 22309173
14.  Severe Preeclampsia and Maternal Self-Report of Oral Health, Hygiene, and Dental Care 
Journal of periodontology  2012;84(2):143-151.
Maternal periodontal disease diagnosed by a detailed oral health examination is associated with preeclampsia. Our objective was to measure the association between maternal self-report of oral symptoms/problems, oral hygiene practices, and/or dental service utilization prior to or during pregnancy and severe preeclampsia.
A written questionnaire was administered to pregnant women at the time of prenatal ultrasound, and outcomes ascertained by chart abstraction. Chi square test compared maternal oral symptoms/problems, hygiene practices, and dental service utilization between women with severe preeclampsia versus normotensive women. Multivariable logistic regression was used to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for severe preeclampsia. Results: 48 (10%) of 470 women reported ≥ 2 oral symptoms/problems in the 6 months prior to pregnancy and 77 (16%) since pregnancy. 51(11%) reported prior periodontal treatment. 28 (6%) of 470 developed severe preeclampsia. Women with a history of periodontal treatment were more likely to develop severe preeclampsia (aOR, 95%CI: 3.71, 1.40-9.83) than women without a prior history of periodontal treatment. Self-reported oral health symptoms/problems, oral hygiene practices, or dental service utilization prior to or during pregnancy were not associated with severe preeclampsia when considered in the context of other maternal risk factors. Conclusion: Maternal self report of previous periodontal treatment prior to pregnancy is associated with severe preeclampsia.
PMCID: PMC3685176  PMID: 22509752
Pregnancy complications; periodontitis; epidemiology
15.  Stimulation of Periodontal Ligament Stem Cells by Dentin Matrix Protein 1 Activates Mitogen-Activated Protein Kinase and Osteoblast Differentiation 
Journal of periodontology  2012;84(3):389-395.
Periodontitis can ultimately result in tooth loss. Many natural and synthetic materials have been tried to achieve periodontal regeneration, but the results remain variable and unpredictable. We hypothesized that exogenous treatment with dentin matrix protein 1 (DMP1) activates specific genes and results in phenotypic and functional changes in human periodontal ligament stem cells (hPDLSCs).
hPDLSCs were isolated from extracted teeth and cultured in the presence or absence of DMP1. Quantitative polymerase chain reactions were performed to analyze the expression of several genes involved in periodontal regeneration. hPDLSCs were also processed for immunocytochemical and Western blot analysis using phosphorylated extracellular signal-regulated kinase (pERK) and ERK antibodies. Alkaline phosphatase and von Kossa staining were performed to characterize the differentiation of hPDLSCs into osteoblasts. Field emission scanning electron microscopic analysis of the treated and control cell cultures were also performed.
Treatment with DMP1 resulted in the upregulation of genes, such as matrix metalloproteinase-2, alkaline phosphatase, and transforming growth factor β1. Activation of ERK mitogen-activated protein kinase signaling pathway and translocation of pERK from the cytoplasm to the nucleus was observed. Overall, DMP1-treated cells showed increased expression of alkaline phosphatase, increased matrix, and mineralized nodule formation when compared with untreated controls.
DMP1 can orchestrate a coordinated expression of genes and phenotypic changes in hPDLSCs by activation of the ERK signaling pathway, which may provide a valuable strategy for tissue engineering approaches in periodontal regeneration.
PMCID: PMC3680598  PMID: 22612367
Bone; bone regeneration; guided tissue regeneration; periodontal; mitogen-activated protein kinases
16.  A Novel Intra-Oral Diabetes Screening Approach in Periodontal Patients: Results of a Pilot Study 
Journal of Periodontology  2011;83(6):699-706.
This pilot study examined whether a novel diabetes screening approach using gingival crevicular blood (GCB) could be used to test for hemoglobin A1c (HbA1c) during the periodontal visit.
At a large periodontics clinic, finger stick blood (FSB) samples from 120 patients as well as GCB samples from those patients with adequate bleeding on probing were collected on special blood collection cards and were analyzed for HbA1c levels in a laboratory. The Pearson correlation coefficient was used to measure correlation between FSB and GCB HbA1c values for 75 paired FSB and GCB samples. A Receiver Operator Characteristic Curve (ROC) analysis was performed to determine an optimal GCB HbA1c criterion value for a positive diabetes screen.
For the 75 paired samples, the Pearson correlation coefficient was .842. The ROC analysis identified a criterion value of 6.3% for the GCB HbA1c test with high sensitivity (.933) and high specificity (.900) corresponding to FSB HbA1c values of 6.5% or greater (in the diabetes range). Using this GCB HbA1c criterion value for 27 additional paired samples in which there was an unidentified component observed to co-elute within the elution window of GCB HbA1c in the laboratory, there was agreement between FSB and GCB values for 24 of the pairs according to whether they were both within, or both outside of the diabetes range.
Using a criterion value of 6.3%, GCB samples are acceptable for HbA1c testing to screen for diabetes in most persons with bleeding on probing at the GCB collection site.
PMCID: PMC3356789  PMID: 22087806
diabetes mellitus; periodontitis; public health dentistry
17.  Comparisons of Subgingival Microbial Profiles of Refractory Periodontitis, Severe Periodontitis and Periodontal Health using the Human Oral Microbe Identification Microarray (HOMIM) 
Journal of periodontology  2009;80(9):1421-1432.
This study compared the subgingival microbiota of subjects with refractory periodontitis (RP) to those in subjects with treatable periodontitis (GR) or periodontal health (PH) using the Human Oral Microbe Identification Microarray (HOMIM).
At baseline, subgingival plaque samples were taken from 47 periodontitis and 20 PH individuals, and analyzed for the presence of 300 species by HOMIM. The periodontitis subjects were classified as RP (n=17) based on mean attachment loss (AL) and/or >3 sites with AL ≥2.5 mm after SRP, surgery and systemically administered amoxicillin and metronidazole or as GR (n=30) based on mean attachment gain and no sites with AL ≥2.5 mm after treatment. Significant differences in taxa among groups were sought using the Kruskal Wallis and Chi-square tests.
More species were detected in diseased patients (GR or RP) than those without disease (PH). RP subjects were distinguished from GR and PH by a significantly high frequency of putative periodontal pathogens such as, Parvimonas micra, Campylobacter gracilis, Eubacterium nodatum, Selenomonas noxia, Tannerella forsythia, Porphyromonas gingivalis, Prevotella spp., Treponema spp., Eikenella corrodens, as well as “unusual” species (Pseudoramibacter alactolyticus, TM7 spp. oral taxon (OT) 346/356, Bacteroidetes spp. OT 272/274, Solobacterium moorei, Desulfobulbus sp. OT 041, Brevundimonas diminuta, Sphaerocytophaga sp. OT 337, Shuttleworthia satelles, Filifactor alocis, Dialister invisus/pneumosintes, Granulicatella adiacens, Mogibacterium tidmidum, Veillonella atypica, Mycoplasma salivarium, Synergistes sp. cluster II, Acidaminococcaceae [G-1] sp. OT 132/150/155/148/135) [p<0.05]. Species that were more prevalent in PH than in periodontitis patients included Actinomyces sp. OT 170, Actinomyces spp. cluster I, Capnocytophaga sputigena, Cardiobacterium hominis, Haemophilus parainfluenzae, Lautropia mirabilis, Propionibacterium propionicum, Rothia dentocariosa/mucilagenosa, Streptococcus sanguinis (p<0.05).
RP patients present a distinct microbial profile compared to patients in the GR and PH groups as determined by HOMIM.
PMCID: PMC3627366  PMID: 19722792
Refractory periodontitis; subgingival microbiota; periodontal pathogen; HOMIM; periodontal therapy
18.  Validity of Partial Protocols to Assess the Prevalence of Periodontal Outcomes and Associated Sociodemographic and Behavior Factors in Adolescents and Young Adults 
Journal of periodontology  2011;83(3):369-378.
Most studies comparing prevalence of periodontal disease and risk factors by using partial protocols were performed in adult populations, with several studies being conducted in clinical settings. The aim of this study is to assess the accuracy of partial protocols in estimating the prevalence of periodontal outcomes in adolescents and young adults from two population-based birth cohorts from Pelotas, Brazil, and to assess differences in the estimation and strength of the effect measures when partial protocols are adopted compared to full-mouth examination.
Gingival bleeding at probing among adolescents (n = 339) and young adults (n = 720) and dental calculus and periodontal probing depth among young adults were assessed using full-mouth examinations and four partial protocols: Ramfjord teeth (RT), community periodontal index (CPI), and two random diagonal quadrants (1 and 3, 2 and 4). Socioeconomic, demographic, and periodontal health-related variables were also collected. Sensitivity, absolute and relative bias, and inflation factors were calculated. Prevalence ratio for each periodontal outcome for the risk factors was estimated.
Two diagonal quadrants showed better accuracy; RT had the worst, whereas CPI presented an intermediate pattern when compared to full-mouth examination. For bleeding assessment in adolescence, RT and CPI underestimated by 18.4% and 16.2%, respectively, the true outcome prevalence, whereas among young adults, all partial protocols underestimated the prevalence. All partial protocols presented similar magnitude of association measures for all investigated periodontal potential risk factors.
Two diagonal quadrants protocol may be effective in identifying the risk factors for the most relevant periodontal outcomes in adolescence and in young adulthood.
PMCID: PMC3605763  PMID: 21859320
Data collection; epidemiologic studies; periodontal index
19.  Autoreactivity of Serum Immunoglobulin to Periodontal Tissue Components: A Pilot Study 
Journal of periodontology  2009;80(4):625-633.
Periodontal diseases are inflammatory diseases resulting in the destruction of tissues of the periodontium. Although bacteria must be present for periodontal disease to occur, a susceptible host is also required, which is determined by genetic, environmental, and acquired factors. One such factor, autoimmunity, may play a role in the tissue destruction. Data indicate that some antibodies that occur in the gingival lesion are directed to host tissue components, such as type I collagen, although investigations of other periodontal autoimmune targets are limited.
Histologic sections and extracts from periodontally healthy teeth and the associated soft tissues were probed with serum from localized aggressive periodontitis (LAgP), chronic periodontitis (CP), and periodontally healthy subjects to determine autoreactivity to components of the periodontium. Any autoreactivity observed was characterized further by mass spectrometry and enzyme-linked immunosorbent assay.
Autoreactivity to components of the periodontium was observed in CP and LAgP. Known autoimmune targets, such as collagen and heat shock protein, were identified along with multiple potential autoimmune targets, including members of the extracellular matrix, such as vimentin, spectrin, filamin, actin, lamin, keratin, and tubulin. Finally, it was determined that the autoreactivity observed in LAgP was more severe and diverse than that observed in CP.
These data demonstrated that autoimmune reactivity can play a role in the tissue destruction of periodontal disease but that the nature of the autoreactivity may differ based on the type and/or stage of periodontal disease.
PMCID: PMC3594842  PMID: 19335083
Antibody; autoimmunity; collagen; periodontal diseases
20.  Heritability of Alveolar Bone Loss from Periodontal Disease in a Baboon Population. A Pilot Study 
Journal of periodontology  2010;82(4):575-580.
Reports from studies of twins, disease aggregation in families, animal models for periodontal disease, and various genetic-analysis studies have determined that genetics plays a role in the susceptibility to periodontal disease. The purpose of this pilot study was to evaluate the effect of genetics on periodontal disease by evaluating the heritability of alveolar bone loss in a captive baboon population.
A collection of baboon skulls from a pedigreed colony (for which scientists and veterinarians maintain complete genealogical and veterinary records) were obtained from the Southwest National Primate Research Center and used in this pilot study. Measurements of alveolar bone loss were performed on 390 dry baboon skulls. A periodontal probe was used to measure alveolar bone loss. Maximum likelihood methods (designed to handle complex genealogies) were used to determine the heritability of alveolar bone loss. This software utilized known pedigrees in the captive baboon sample and tested the relationship between pairwise kinship and alveolar bone loss data to determine the heritability of alveolar bone loss from periodontal disease.
Genetic data were available for 347 of the 390 specimens. Using age and sex as covariates, genetic analysis indicated a heritability of 35% (standard error=20%, p=0.01). While sex was not a significant factor in periodontal disease (p=0.96), age was highly significantly associated with periodontal disease (p<0.0001).
In this pilot study, analysis of alveolar bone loss measurements from captive baboons indicates that bone loss increases with age and that a portion of periodontal disease risk may be due to genetic variance. These findings provide evidence that periodontal disease is heritable in captive baboons and indicate that a larger, more-detailed study is warranted.
PMCID: PMC3575216  PMID: 21043800
periodontitis; alveolar bone; genetics; baboons
21.  Periodontal disease, hypertension and blood pressure among older adults in Puerto Rico 
Journal of periodontology  2012;84(2):203-211.
Current scientific evidence addressing the relation between periodontitis and hypertension is limited to a few studies producing inconsistent results.
All participants of an on-going representative cohort of Puerto Rican elderly who were 70 years and older and residing in San Juan metropolitan area were invited to this cross-sectional study. Periodontal probing depth (PD) and attachment loss (AL) were summarized using CDC-AAP definition for severe periodontitis (≥2 teeth with AL ≥6mm and ≥1 tooth with PD ≥5mm). We averaged three repeated blood pressure (BP) measurements taken using a standardized auscultatory method. Information on hypertension history, use of anti-hypertensive medications and potential confounders (age, gender, smoking, heavy and binge drinking, diabetes, utilization of preventive dental services, flossing, body mass index, fruit and vegetable, whole wheat bread and high-fiber cereal consumption) was collected during in-person interviews. High BP was defined as average systolic BP ≥140 mmHg or diastolic ≥90 mmHg. Multivariate logistic regression models were used to study the relation between severe periodontitis, hypertension history and high BP.
The study population comprised 182 adults. In multivariate analysis, there was no association between severe periodontitis and hypertension history (OR=0.99, 95% CI: 0.40–2.48). Severe periodontitis was associated with high BP, with OR of 2.93 (95% CI: 1.25–6.84), after adjusting for age, gender, smoking, and binge drinking. This association was stronger when restricted to those with hypertension or taking anti-hypertensive medications: OR=4.20 (95% CI: 1.28–13.80).
Our results suggest that periodontitis may contribute to poor blood pressure control among older adults.
PMCID: PMC3561508  PMID: 22548584
Periodontal diseases; periodontitis; hypertension; blood pressure
22.  Relationship Between Conversion of Localized Juvenile Periodontitis-Susceptible Children From Health to Disease and Actinobacillus actinomycetemcomitans Leukotoxin Promoter Structure* 
Journal of periodontology  1998;69(9):998-1007.
The periodontal pathogen Actinobacillus actinomycetemcomitans produces a leukotoxin that is considered a primary virulence factor in localized juvenile Periodontitis (LJP). Select strains of the bacterium contain a 530-bp deletion in the promoter region of the leukotoxin gene operon which results in enhanced transcription of the leukotoxin. DNA hybridization and polymerase chain reaction (PCR) were used to examine genetic variants of A. actinomycetemcomitans in 24 LJP-susceptible children from 21 families having a history of the disease and 34 control children from non-LJP families. A significant association was found between the detection of variants that had a deletion in the leukotoxin promoter region, indicative of a high level expression leukotoxin genotype, and conversion from a healthy periodontal status to disease. Subjects harboring A. actinomycetemcomitans of this genotype were more likely to convert to LJP than those subjects who had variants containing the full length leukotoxin promoter region (odds ratio = 22.50, 95% C.I.). These findings support the concept that highly virulent strains or clonal types of periodontal pathogens play a major role in the initiation of periodontal disease in susceptible hosts.
PMCID: PMC3523333  PMID: 9776028
Periodontitis; juvenile/epidemiology; Actinobacillus actinomycetemcomitans; leukotoxin; epidemiology; polymerase chain reaction; polymorphism; restriction fragment length
23.  Development of an Animal Model for Aggregatibacter Actinomycetemcomitans Biofilm-Mediated Oral Osteolytic Infection: A Preliminary Study 
Journal of periodontology  2011;82(5):778-789.
Biofilm-induced inflammatory osteolytic oral infections, such as periodontitis and peri-implantitis, have complex etiology and pathogenesis. A significant obstacle to research has been the lack of appropriate animal models where the inflammatory response to biofilms can be investigated. The aim of this study is to develop a novel animal model to study the host response to Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans)–biofilm colonizing titanium implants.
Titanium implants were inoculated in vitro with A. actinomycetemcomitans, establishing a biofilm for 1 to 3 days. Biofilm-inoculated and control implants were transmucosally placed into rat hard palate or alveolar ridge. Analysis included documentation of clinical inflammation, polymerase chain reaction, and culture detection of A. actinomycetemcomitans and microcomputed tomography quantitation of peri-implant bone volume.
Viable A. actinomycetemcomitans biofilm was successfully established on titanium implants in vitro, detected by confocal laser scanning microscopy. An inflammatory response characterized by clinical inflammation, bleeding, ulceration, hyperplasia, and necrosis was observed around biofilm-inoculated implants. A. actinomycetemcomitans was detected by polymerase chain reaction and culture analysis on 100%of biofilm-inoculated implants for up to 3 weeks and 25%for up to 6 weeks. Microcomputed tomography analysis demonstrated significantly lower bone volume (P <0.05) around biofilm-inoculated implants (29.6% ± 7.6%) compared to non-inoculated implants (50.5% ± 9.6%) after 6 weeks.
These results describe a novel animal model where A. actinomycetemcomitans biofilm was established in vitro on titanium implants before placement in rat oral cavity, leading to an inflammatory response, osteolysis, and tissue destruction. This model may have potential use for investigation of host responses to biofilm pathogens and antibiofilm therapy.
PMCID: PMC3496747  PMID: 21222546
Aggregatibacter actinomycetemcomitans; biofilms; dental implants; infection; models; animal; rats
24.  Bacterial Lysine Decarboxylase Influences Human Dental Biofilm Lysine Content, Biofilm Accumulation and Sub-Clinical Gingival Inflammation 
Journal of periodontology  2011;83(8):1048-1056.
Dental biofilms contain a protein that inhibits mammalian cell growth, possibly lysine decarboxylase from Eikenella corrodens. This enzyme decarboxylates lysine, an essential amino acid for dentally attached cell turnover in gingival sulci. Lysine depletion may stop this turnover, impairing the barrier to bacterial compounds. The aims of this study were to determine biofilm lysine and cadaverine contents before oral hygiene restriction (OHR), and their association with plaque index (PI) and gingival crevicular fluid (GCF) after OHR for a week.
Laser-induced fluorescence after capillary electrophoresis was used to determine lysine and cadaverine contents in dental biofilm, tongue biofilm and saliva before OHR and in dental biofilm after OHR.
Before OHR, lysine and cadaverine contents of dental biofilm were similar and 10-fold greater than in saliva or tongue biofilm. After a week of OHR, the biofilm content of cadaverine increased and that of lysine decreased, consistent with greater biofilm lysine decarboxylase activity. Regression indicated that PI and GCF exudation were positively related to biofilm lysine post-OHR, unless biofilm lysine exceeded the minimal blood plasma content in which case PI was further increased but GCF exudation was reduced.
After OHR, lysine decarboxylase activity seems to determine biofilm lysine content and biofilm accumulation. When biofilm lysine exceeds minimal blood plasma content after OHR, less GCF appeared despite more biofilm. Lysine appears important for biofilm accumulation and the epithelial barrier to bacterial proinflammatory agents.
Clinical Relevance
Inhibiting lysine decarboxylase may retard the increased GCF exudation required for microbial development and gingivitis.
PMCID: PMC3415560  PMID: 22141361
Gingival crevicular fluid; Gingivitis; Oral hygiene; Pathogenesis of periodontal disease(s); Microbiology
25.  One-year Effects of Vitamin D and Calcium Supplementation on Chronic Periodontitis 
Journal of periodontology  2010;82(1):25-32.
We previously reported in a cross-sectional study that patients who were in periodontal maintenance programs and were taking vitamin D and calcium supplementation had a trend for better periodontal health compared with patients not taking supplementation. The objective of the present study was to determine, for the same group of subjects, whether there was a difference in periodontal health over a one–year period.
Fifty-one patients enrolled in maintenance programs from two dental clinics were recruited. Twenty-three were taking vitamin D (≥400 international units/day) and calcium (≥1000mg/day) supplementation, and twenty-eight were not taking supplementation. All subjects had ≥2 interproximal sites with ≥3 mm clinical attachment loss. For mandibular-posterior teeth, these clinical parameters were recorded: gingival index, plaque index, probing depth, attachment loss, bleeding upon probing, calculus index and furcation involvement. Photostimulable-phosphor, posterior bitewing radiographs were taken to assess alveolar bone. Daily vitamin D and calcium intakes were estimated by nutritional analysis. Data were collected at baseline, 6 months, and 12 months.
Clinical parameters improved with time in both groups (p<0.01). When clinical measures were considered collectively, the results were borderline significant at baseline (p=0.061), significant at 6 months (p=0.049) but not significant at 12 months (p=0.114). After adjusting for covariates, the effect of supplements was significant at baseline (p=0.037), borderline at 6 months (p=0.058) and not significant at 12 months (p=0.142)
Calcium and vitamin D supplementation has a modest positive effect on periodontal health, and consistent dental care improves clinical parameters of periodontal disease regardless of such supplements. Calcium and vitamin D supplementation has a modest positive effect on periodontal health, and consistent dental care improves clinical parameters of periodontal disease regardless of such supplements. Our findings raise the possibility that vitamin D, perhaps at higher doses, may positively impact on periodontal disease severity.
PMCID: PMC3472001  PMID: 20809866
vitamin D; calcium; chronic periodontitis; alveolar bone

Results 1-25 (97)