bluuebunny/crossref_metadata_2025 huggingface dataset:
Responses of the Human Submandibular Artery to ACh and VIP
Authors: Stojić D. , Pešić S. , Radenković M. , Popović-Roganović J. , Pešić Z. , Grbović L.
Published: January 2009

Endothelial vasodilatory substances may play a central role in the local regulation of vascular tone. We hypothesized that these substances can mediate endothelium-dependent vasodilatory responses to acetylcholine (ACh) and vasoactive intestinal peptide (VIP) in the human submandibular artery. We evaluated the contributions of endothelial vasodilatory substances to vessel relaxation in response to ACh and VIP, using different inhibitors of endothelial vasodilation, the nitric oxide synthase inhibitor, the cyclo-oxygenase inhibitor, indomethacin, the potassium channel blocker, and 4-aminopyridine. ACh and VIP caused an endothelium- and concentration-dependent relaxation in this artery. ACh relaxation was completely blocked after the concomitant addition of NG-nitro-L-arginine and indomethacin. The vasorelaxant effect of ACh was not influenced by 4-aminopyridine. VIP relaxation was almost completely abolished by 4-aminopyridine, and was partly inhibited by NG-nitro-L-arginine, but was not affected by indomethacin. Thus, in the human submandibular artery, ACh and VIP produced endothelium-dependent vasodilation with different underlying mechanisms: release of nitric oxide (NO) and cyclo-oxygenase products for ACh, and release of NO and endothelium-derived hyperpolarizing factor for VIP.
Effect of Facial Sensory Re-training on Sensory Thresholds
Authors: Essick G.K. , Phillips C. , Zuniga J.
Published: January 2009

Nearly 100% of patients experience trauma to the trigeminal nerve during orthognathic surgery, impairing sensation and sensory function on the face. In a recent randomized clinical trial, people who performed sensory re-training exercises reported less difficulty related to residual numbness and decreased lip sensitivity than those who performed standard opening exercises only. We hypothesized that re-training reduces the impaired performance on neurosensory tests of tactile function that is commonly observed post-surgically. We analyzed thresholds for contact detection, two-point discrimination, and two-point perception, obtained during the clinical trial before and at 1, 3, and 6 months after surgery, to assess tactile detection and discriminative sensitivities, and subjective interpretation of tactile stimulation, respectively. Post-surgery, the retrained persons exhibited less impairment, on average, than non-retrained persons only in two-point perception (P < 0.025), suggesting that retrained persons experienced or interpreted the tactile stimuli differently than did non-retrained persons.
Interleukin 18 and Periodontal Disease
Authors: Orozco A. , Gemmell E. , Bickel M. , Seymour G.J.
Published: January 2009

Cytokines are of major importance in periodontal disease progression. It is generally agreed that control of the Th1/Th2 balance is central to the immunoregulation of periodontal disease. There is increasing evidence in humans that the stable periodontal lesion is mediated by Th1 cells, while the progressive lesion sees a shift toward Th2 cells. Equally, there is conflicting evidence, mainly in animal models, that bone loss is mediated by Th1 responses, and that Th2 responses are protective. In the presence of IL-12, IL-18 induces Th1 responses while, in the absence of IL-12, it promotes Th2 responses. It is clear, therefore, that since IL-18 has the ability to induce either Th1 or Th2 differentiation, it becomes important to consider its role in periodontal disease. This review endeavors to give an overview of this cytokine and its relevance for periodontal disease.
Human Hertwig’s Epithelial Root Sheath Cells Play Crucial Roles in Cementum Formation
Authors: Sonoyama W. , Seo B.-M. , Yamaza T. , Shi S.
Published: January 2009

Hertwig’s epithelial root sheath (HERS) cells are a unique population of epithelial cells in the periodontal ligament compartment. To date, their functional role has not been fully elucidated. Our hypothesis was that HERS cells may be involved in regulating differentiation of periodontal ligament stem cells (PDLSCs) and forming cementum in vivo. In this study, we found that HERS cells may be capable of promoting PDLSC differentiation and undergoing epithelial-mesenchymal transition in vitro. Immunohistochemical staining, Western blot analysis, a transwell co-culture system, and in vivo transplantation were used to characterize the interplay between HERS cells and PDLSCs, as well as the epithelial-mesenchymal transition (EMT) of HERS cells. TGFβ1 was capable of inducing the epithelial-mesenchymal transition of HERS cells through activating the PI3K/AKT pathway. Furthermore, HERS cells were able to form cementum-like tissue when transplanted into immunocompromised mice. Abbreviations: bone marrow mesenchymal stem cell, BMMSC; bone sialoprotein, BSP; hydroxyapatite/tricalcium phosphate, HA/TCP; Hertwig’s epithelial root sheath, HERS; osteocalcin, OCN; periodontal ligament, PDL; periodontal ligament stem cell, PDLSC; phosphatidylinositol 3-kinase, PI3K.
Dioxin Alters Gene Expression in Mouse Embryonic Tooth Explants
Authors: Sahlberg C. , Peltonen E. , Lukinmaa P.-L. , Alaluusua S.
Published: January 2009

Dioxins are ubiquitous environmental poisons that cause disturbances in developing organs, including the teeth. Exposure to 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) at the cap stage leads to reduced tooth size and deformation of cuspal morphology. Our hypothesis was that TCDD affects the expression of genes specific for tooth development, which leads to these aberrations. Mouse embryonic E14 tooth germs were cultured for 24 hrs with/without 1 μM TCDD. Analysis of total RNA on Affymetrix arrays showed that TCDD altered the expression of 31 known genes by a fold factor of at least 2. Genes implied in tooth development expressed only slight changes. Genes active at the cap stage were selected for quantitative PCR analysis. Of these, the most highly up-regulated were Follistatin and Runx2, while TGFβ 1 and p21 were the most down-regulated genes. Incomplete tooth morphogenesis caused by TCDD may thus result from modified expression of developmentally regulated genes.
Detachment and Killing of Aggregatibacter actinomycetemcomitans Biofilms by Dispersin B and SDS
Authors: Izano E.A. , Wang H. , Ragunath C. , Ramasubbu N. , Kaplan J.B.
Published: January 2009

The periodontopathogen Aggregatibacter actinomycetemcomitans forms tenacious biofilms on abiotic surfaces in vitro. The objective of the present study was to measure the susceptibility of A. actinomycetemcomitans biofilms to detachment and killing by the anionic surfactant sodium dodecyl sulfate (SDS). We found that biofilms formed by a wild-type strain were resistant to detachment by SDS. In contrast, biofilms formed by an isogenic mutant strain that was deficient in the production of PGA (poly- N-acetyl-glucosamine), a biofilm matrix polysaccharide, were sensitive to detachment by SDS. Pre-treatment of wild-type biofilms with dispersin B, a PGA-degrading enzyme, rendered them sensitive to detachment by SDS and resulted in a > 99% increase in SDS-mediated cell killing. We concluded that PGA protects A. actinomycetemcomitans cells from detachment and killing by SDS. Dispersin B and SDS may be useful agents for treating chronic infections caused by A. actinomycetemcomitans and other PGA-producing bacteria.
Force-induced IL-8 from Periodontal Ligament Cells Requires IL-1β
Authors: Maeda A. , Soejima K. , Bandow K. , Kuroe K. , Kakimoto K. , Miyawaki S. , Okamoto A. , Matsuguchi T.
Published: January 2009

During orthodontic tooth movement, mechanical stresses induce inflammatory reactions in the periodontal ligament (PDL). We hypothesized that chemokines released from PDL cells under mechanical stress regulate osteoclastogenesis, and investigated the profiles and mechanisms of chemokine expression by human PDL cells in response to mechanical stress. In vitro, shear stress and pressure force rapidly increased the gene and protein expressions of IL-8/CXCL8 by PDL cells. Consistently, amounts of IL-8 in the gingival crevicular fluid of healthy individuals increased within 2 to 4 days of orthodontic force application. The PDL cells constitutively expressed low levels of IL-1β, which were not further increased by mechanical stress. Interestingly, neutralization of IL-1β abolished IL-8 induction by mechanical stresses, indicating that IL-1β is essential for IL-8 induction, presumably though autocrine or paracrine mechanisms. Finally, experiments with signal-specific inhibitors indicated that MAP kinase activation is essential for IL-8 induction.
RCT Comparing Posterior Occlusal Forms for Complete Dentures
Authors: Sutton A.F. , Worthington H.V. , McCord J.F.
Published: January 2009

Complete dentures can be produced with different types of occlusal forms. There is some evidence to suggest that it may be advantageous to provide complete dentures with cusped posterior teeth. The aim of this research was to compare the levels of subject satisfaction with 3 types of posterior occlusal forms for complete dentures, in a randomized cross-over trial design. Forty-five participants were randomly assigned 3 sets of complete dentures with different posterior occlusal forms (zero-degree, anatomic, and lingualized occlusions). Subjective data were collected according to visual analogue scales after 8 weeks of denture-wearing. Statistical analysis consisted of repeated-measures analysis of variance, followed by paired t tests. Lingualized and anatomic occlusal forms were perceived to be significantly superior in terms of chewing ability, when compared with zero-degree posterior occlusal surfaces.
Gel Phase Formation at Resin-modified Glass-ionomer/Tooth Interfaces
Authors: Coutinho E. , Yoshida Y. , Inoue S. , Fukuda R. , Snauwaert J. , Nakayama Y. , De Munck J. , Lambrechts P. , Suzuki K. , Van Meerbeek B.
Published: January 2009

Ionic bonding between polyalkenoic acid and hydroxyapatite may explain the excellent bonding retention of glass-ionomers in clinical trials. We have here investigated the extent to which the self-adhesiveness of resin-modified glass-ionomers (RMGIs) can be attributed to this chemical bonding capacity. Therefore, the interaction of 3 RMGIs with tooth substrates was comprehensively characterized, with electron and atomic force microscopy correlated with x-ray photoelectron spectroscopy (XPS). Interfacial ultrastructural analysis for 2 RMGIs disclosed a shallow hybridization of hydroxyapatite-coated collagen, on which a submicron gel phase was deposited through reaction of the polyalkenoic acid with calcium extracted from the dentin surface. One RMGI, however, bonded to dentin without hybrid layer or gel phase formation. XPS indicated that polycarboxylic acids included in the RMGIs electrostatically interacted with hydroxyapatite. We conclude that the self-adhesiveness of RMGIs should be attributed to ionic bonding to hydroxyapatite around collagen, and to micro-mechanical interlocking for those RMGIs that additionally hybridize dentin.
Resin Infiltration of Natural Caries Lesions
Authors: Paris S. , Meyer-Lueckel H. , Kielbassa A.M.
Published: January 2009

Infiltration of non-cavitated caries lesions with light-curing resins could lead to an arrest of lesion progression. The aim of this study was to evaluate the penetration of a conventional adhesive into natural enamel caries after pre-treatment with two different etching gels in vitro. Extracted human molars and premolars showing proximal white-spot lesions were cut across the lesions perpendicular to the surface. Corresponding lesion halves were etched for 120 sec with either 37% phosphoric acid gel (H3PO4) or 15% hydrochloric acid gel (HCl), and subsequently infiltrated with an adhesive. Specimens were observed by confocal microscopy. Mean penetration depths (SD) in the HCl group [58 (37) μm] were significantly increased compared with those of the H3PO4 group [18 (11) μm] (p < 0.001; Wilcoxon). It can be concluded that etching with 15% hydrochloric acid gel is more suitable than 37% phosphoric acid gel as a pre-treatment for caries lesions intended to be infiltrated.
Effect of Reinforcement on Overdenture Strain
Authors: Gonda T. , Ikebe K. , Dong J. , Nokubi T.
Published: January 2009

Because the abutment becomes the fulcrum, and the denture base over the coping is usually thin, the overdenture is susceptible to fracture. We hypothesized that rational reinforcement can reduce strain and prevent deformation and fracture of the overdenture. We investigated the effect of reinforcement on overdenture strain around the copings and at a midline. A mandibular edentulous model with a 2-mm-thick artificial mucosa and abutment teeth installed bilaterally in the canine position was produced. The coping had a dome-shaped upper surface with a height of 6 mm. On the lingual polished surface, strain gauges were attached at the canine position and at the midline. A vertical load of 49 N was applied on the occlusal surface. Among several kinds of reinforcements, the cast metal reinforcement that covers both the midline and the coping top significantly reduced the strain on the overdenture. It is suggested that this simple reinforcement is effective in preventing deformation and fracture of the overdenture.
Quality of Life and Disability Weights Associated with Periodontal Disease
Authors: Brennan D.S. , Spencer A.J. , Roberts-Thomson K.F.
Published: January 2009

Burden-of-oral-disease studies have been hampered by lack of data on disability weights. It is likely that disability weights will vary between conditions such as gingivitis and periodontal pockets. The aims of this study were to assess health-related quality of life and disability weights for periodontal conditions. A random sample of 45- to 54-year-olds was surveyed during 2004-05 (n = 879, response rate = 43.8%), with oral examinations on n = 709 persons (completion rate = 80.7%). Oral disease symptoms were recorded by the EuroQol, from which disability weights were calculated. Reported pain/discomfort ranged from 6.1% of persons (gingivitis) to 25.8% of persons (6+ mm pockets). Lower disability weights were associated with gingivitis (0.001) and 6+ mm gingival recession (0.004), with higher weights for 6+ mm loss of attachment (0.012) and 6+ mm pocket depth (0.018). Variation in symptom experience indicated the need for investigators to identify periodontal conditions and apply appropriate disability weights in burden-of-disease studies.
Post Placement Affects Survival of Endodontically Treated Premolars
Authors: Ferrari M. , Cagidiaco M.C. , Grandini S. , De Sanctis M. , Goracci C.
Published: January 2009

Clinical evidence is lacking regarding the influence of the amount of residual coronal dentin and of post placement on the failure risk of endodontically compromised teeth. The aim of this prospective clinical trial was to assess whether these factors significantly affect the two-year survival of restored pulpless premolars. A sample of 210 individuals provided six experimental groups of 40 premolars in need of endodontic treatment. Groups were defined based on the amount of dentin left at the coronal level. Within each group, in half of the teeth selected at random, a fiber post was inserted inside the root canal, whereas in the remaining half of the premolars, no post was placed. All teeth were covered with a crown. The Cox regression analysis revealed that post placement resulted in a significant reduction of failure risk (p < 0.001). Failure risk was increased for teeth under the “no ferrule” (p = 0.001) and “ferrule effect” conditions (p = 0.004).
Novel Mutations of Cathepsin C Gene in Two Chinese Patients with Papillon-Lefèvre Syndrome
Authors: Yang Y. , Bai X. , Liu H. , Li L. , Cao C. , Ge L.
Published: January 2009

Papillon-Lefèvre syndrome (PLS) is an inherited human disease characterized by early-onset periodontitis and palmoplantar hyperkeratosis. Mutations of the lysosomal protease cathepsin C ( CTSC) gene have been shown to be the genetic cause of Papillon-Lefèvre syndrome. There are several case reports in China, while there has been no study on the genetic analysis of PLS. We studied two Chinese patients carrying Papillon-Lefèvre syndrome and showing premature tooth loss and palmoplantar hyperkeratosis. Mutation screening and sequence analysis of the CTSC gene revealed a compound heterozygous mutation (c.415 G>A and c.778 T>C) in one patient, and two novel compound heterozygous mutations (c.851G>A and c.112delCCTG) in the other patient. Our novel discovery indicates that the phenotypes observed in these two patients are due to the CTSC gene mutation.
Joining Veneers to Ceramic Cores and Dentition with Adhesive Interlayers
Authors: Lee J.J.-W. , Wang Y. , Lloyd I.K. , Lawn B.R.
Published: January 2009

Adhesive joining of veneers to cores offers potential simplicity and economy in the fabrication of all-ceramic crowns. We tested the hypothesis that resin-based adhesives can be used for such fabrication without compromising mechanical integrity of the crown structure. A simple test procedure for quantifying this hypothesis was proposed. A model glass veneer layer 1 mm thick (representative of porcelain), adhesively bonded onto a glass-like core substrate (ceramic or dental enamel), was loaded at its top surface with a hard sphere (occlusal force) until a radial crack initiated at the veneer undersurface. The critical loads for fracture, visually observable in the transparent glass, afforded a measure of the predisposition for the adhesive to cause veneer failure in an occlusal overload. Two adhesives were tested, one a commercial epoxy resin and the other a relatively stiff in-house-developed composite. The results confirmed that stiffer adhesives provide higher resistance to failure.
Antimicrobial Effect of Nanometric Bioactive Glass 45S5
Authors: Waltimo T. , Brunner T.J. , Vollenweider M. , Stark W.J. , Zehnder M.
Published: January 2009

Most recent advances in nanomaterials fabrication have given access to complex materials such as SiO2-Na2O-CaO-P2O5 bioactive glasses in the form of amorphous nanoparticles of 20- to 60-nm size. The clinically interesting antimicrobial properties of commercially available, micron-sized bioactive glass 45S5 have been attributed to the continuous liberation of alkaline species during application. Here, we tested the hypothesis that, based on its more than ten-fold higher specific surface area, nanometric bioactive glass releases more alkaline species, and consequently displays a stronger antimicrobial effect, than the currently applied micron-sized material. Ionic dissolution profiles were monitored in simulated body fluid. Antimicrobial efficacy was assessed against clinical isolates of enterococci from persisting root canal infections. The shift from micron- to nano-sized treatment materials afforded a ten-fold increase in silica release and solution pH elevation by more than three units. Furthermore, the killing efficacy was substantially higher with the new material against all tested strains.
Micelle Structure of Amelogenin in Porcine Secretory Enamel
Authors: Fukae M. , Yamamoto R. , Karakida T. , Shimoda S. , Tanabe T.
Published: January 2009

Even during the secretory stage of amelogenesis, enamel crystals thicken as amelogenins (the major protein component) decrease. To explain this phenomenon, we propose a model for amelogenin structure and function based upon the hypothesis that amelogenin forms micelles. Solubility and hydrophobicity analyses suggest that all but the hydrophilic amelogenin C-terminal regions aggregate via hydrophobic bonds to form a micelle core. Amelogenin micelles may form super-assemblies via their C-termini (KTKREEVD), which contain complementary positive (KTKR) and negative (EEVD) elements. Disassembly of the micelles through controlled proteolysis provides space for crystal growth. Initial cleavage (by enamelysin) removes the surface-accessible amelogenin C-terminus, exposing the middle portion to cleavage (by EMSP1). As a result, the 13-kDa amelogenin, a rod-shaped domain based upon ultrafiltration and transmission electron microscopy studies, is released. This model explains how amelogenin is able to ‘space’ and support the ribbon-like crystals and continuously yield space as the crystals thicken, until they are sufficiently mature to support themselves. Abbreviations: dentino-enamel junction (DEJ), sodium dodecyl sulfate (SDS), polyacrylamide gel electro phoresis (PAGE), transmission electron microscope (TEM).
Dentonin, a MEPE Fragment, Initiates Pulp-healing Response to Injury
Authors: Six N. , Septier D. , Chaussain-Miller C. , Blacher R. , DenBesten P. , Goldberg M.
Published: January 2009

Phosphorylated extracellular matrix proteins, including matrix extracellular phosphoprotein (MEPE), are involved in the formation and mineralization of dental tissues. In this study, we evaluated the potential of Dentonin, a synthetic peptide derived from MEPE, to promote the formation of reparative dentin. Agarose beads, either soaked with Dentonin or unloaded, were implanted into the pulps of rat molars, and examined 8, 15, and 30 days after treatment. At day 8, Dentonin promoted the proliferation of pulp cells, as visualized by PCNA-labeling. RP59-positive osteoblast progenitors were located around the Dentonin-soaked beads. PCNA- and RP59-labeling were decreased at day 15, while osteopontin, weakly labeled at day 8, was increased at 15 days, but dentin sialoprotein was undetectable at any time. At 8 days, precocious reparative dentin formation occurred in pulps containing Dentonin-soaked beads, with formation slowing after 15 days. These results suggest that Dentonin affects primarily the initial cascade of events leading to pulp healing.
p38 Pathway Kinases as Anti-inflammatory Drug Targets
Authors: Schindler J.F. , Monahan J.B. , Smith W.G.
Published: January 2009

Mitogen-activated protein kinases (MAPK) are intracellular signaling molecules involved in cytokine synthesis. Several classes of mammalian MAPK have been identified, including extracellular signal-regulated kinase, c-jun N-terminal kinase, and p38 MAP kinase. p38α is a key MAPK involved in tumor necrosis factor α and other cytokine production, as well as enzyme induction (cyclooxygenase-2, inducible nitric oxide synthase, and matrix metalloproteinases) and adhesion molecule expression. An understanding of the broad biologic and pathophysiological roles of p38 MAPK family members has grown significantly over the past decade, as has the complexity of the signaling network leading to their activation. Downstream substrates of MAPK include other kinases ( e.g., mitogen-activated protein-kinase-activated protein kinase 2) and factors that regulate transcription, nuclear export, and mRNA stability and translation. The high-resolution crystal structure of p38α has led to the design of selective inhibitors that have good pharmacological activity. Despite the strong rationale for MAPK inhibitors in human disease, direct proof of concept in the clinic has yet to be demonstrated, with most compounds demonstrating dose-limiting adverse effects. The role of MAPK in inflammation makes them attractive targets for new therapies, and efforts are continuing to identify newer, more selective inhibitors for inflammatory diseases.
p38 MAPK Signaling in Oral-related Diseases
Authors: Patil C.S. , Kirkwood K.L.
Published: January 2009

Multiple dental diseases are characterized by chronic inflammation, due to the production of cytokines, chemokines, and prostanoids by immune and non-immune cells. Membrane-bound receptors provide a link between the extracellular environment and the initiation of intracellular signaling events that activate common signaling components, including p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor (NF)-κB. Although ERK pathways regulate cell survival and are responsive to extracellular mitogens, p38 MAPK, JNK, and NF-κB are involved in environmental stress responses, including inflammatory stimuli. Over the past decade, significant advances have been made relative to our understanding of the fundamental intracellular signaling mechanisms that govern inflammatory cytokine expression. The p38 MAPK pathway has been shown to play a pivotal role in inflammatory cytokine and chemokine gene regulation at both the transcriptional and the post-transcriptional levels. In this review, we present evidence for the significance of p38 MAPK signaling in diverse dental diseases, including chronic pain, desquamative disorders, and periodontal diseases. Additional information is presented on the molecular mechanisms whereby p38 signaling controls post-transcriptional gene expression in inflammatory states.
Identification of a Sleep Bruxism Subgroup with a Higher Risk of Pain
Authors: Rompré P.H. , Daigle-Landry D. , Guitard F. , Montplaisir J.Y. , Lavigne G.J.
Published: January 2009

Sleep bruxism research diagnostic criteria (SB-RDC) have been applied since 1996. This study was performed to validate these criteria and to challenge the hypothesis that pain is associated with lower frequencies of orofacial activities. Polygraphic recordings were made of 100 individuals presenting with a clinical diagnosis of sleep bruxism and 43 control individuals. TwoStep Cluster analyses (SPSS) were performed with sleep bruxism variables to reveal groupings among sleep bruxers and control individuals. Participants completed questionnaires during screening, diagnosis, and recording sessions. Cluster analysis identified three subgroups of sleep bruxers. Interestingly, 45 of the 46 sleep bruxers with values below SB-RDC were classified in the low-frequency cluster. These individuals were more likely to complain of pain and fatigue of masticatory muscles than were the higher-frequency sleep bruxers (odds ratios > 3.9, p < 0.01). Sleep bruxers were distributed among three heterogeneous groups. Sleep bruxers with low frequencies of orofacial activities were more at risk of reporting pain.
Hop Bract Polyphenols Reduced Three-day Dental Plaque Regrowth
Authors: Shinada K. , Tagashira M. , Watanabe H. , Sopapornamorn P. , Kanayama A. , Kanda T. , Ikeda M. , Kawaguchi Y.
Published: January 2009

Previous research has shown the inhibitory effects of hop bract polyphenols (HBP) on cariogenic streptococci in vitro, but their effects in humans have not been investigated. This double-blind, crossover clinical study tested the hypothesis that HBP delivered in a mouthrinse suppresses plaque regrowth in humans. Twenty-nine healthy male volunteers had all plaque removed, and refrained from all oral hygiene for 3 days, except for rinsing with a mouthrinse containing 0.1% HBP or a placebo. The results showed that the mean amount of plaque assessed by the Patient Hygiene Performance score after the volunteers used the HBP mouthrinse was significantly less than that after they used the placebo (p < 0.001). The number of mutans streptococci in the plaque samples after volunteers used the HBP mouthrinse was significantly lower than that after they used the placebo (p < 0.05). These findings suggested that HBP, delivered in a mouthrinse, successfully reduced dental plaque regrowth in humans.
Inhibition of SFRP1 Reduces Severity of Periodontitis
Authors: Li C.H. , Amar S.
Published: January 2009

Porphyromonas gingivalis ( P. gingivalis) is implicated as a major pathogen in periodontitis, a common infectious disease characterized by the inflammation and destruction of periodontal tissues. Secreted frizzled-related protein 1 (SFRP1) modulates apoptosis in different cell types. To characterize the roles of SFRP1 in periodontitis, we used a P. gingivalis-induced murine periodontitis model. Inflammatory responses were measured by morphometric and histomorphometric analysis, apoptosis assay, and immunohistochemistry. We found that P. gingivalis-infected mouse periodontal tissues expressed significantly more SFRP1 compared with those of control mice. Also, in P. gingivalis-infected animals, more apoptosis of inflammatory cells, fibroblasts, and bone-lining cells was observed compared with controls. Antibody experiments aimed at inhibiting SFRP1 expression in periodontitis resulted in a reduction of periodontal breakdown, inflammatory cell infiltrate, osteoclastogenesis, and apoptosis of inflammatory cells and fibroblasts. The results of our studies suggest that SFRP1 may be involved in the development of periodontitis, since inhibiting SFRP1 resulted in reduced periodontal breakdown.
Hemoglobin and LPS Act in Synergy to Amplify the Inflammatory Response
Authors: Bodet C. , Chandad F. , Grenier D.
Published: January 2009

Vascular disruption and bleeding during periodontitis likely increase the levels of hemoglobin in gingival crevicular fluid. The aim of this study was to investigate the effect of hemoglobin on the inflammatory responses of human macrophages stimulated with lipopolysaccharides (LPS) isolated from periodontopathogens. The production of interleukin-1 beta (IL-1β), IL-6, IL-8, and tumor necrosis factor alpha (TNF-α) by macrophages following challenges with Porphyromonas gingivalis and Fusobacterium nucleatum LPS in the presence or absence of human hemoglobin was analyzed by ELISA. The effect of hemoglobin on LPS-binding to macrophages was evaluated with 3H-LPS. Hemoglobin and LPS from periodontopathogens acted in synergy to stimulate the production of high levels of IL-1β, IL-6, IL-8, and TNF-α by macrophages. Hemoglobin also enhanced LPS-binding to macrophages. This study suggests that hemoglobin contributes to increases in the levels of pro-inflammatory mediators in periodontal sites by acting in synergy with LPS from periodontopathogens, thus favoring the progression of periodontitis.
VIP Inhibits P. gingivalis LPS-induced IL-18 and IL-18BPa in Monocytes
Authors: Foster N. , Andreadou K. , Jamieson L. , Preshaw P.M. , Taylor J.J.
Published: January 2009

IL-18 is a pro-inflammatory cytokine that is important in the regulation of T-cells and is elevated in inflammatory disorders such as periodontal disease. Vasoactive intestinal peptide (VIP) modulates immune responses to the periodontal pathogen Porphyromonas gingivalis ( Pg). Our objective was to investigate the effect of Pg LPS on IL-18 and its natural inhibitor, IL-18 binding protein (IL-18BPa), in human monocytes, and the effect of VIP on this system. We demonstrated that Pg LPS induced both IL-18 and IL-18BPa secretion in cultures of the human monocytic cell line THP-1, as measured by specific ELISA. The addition of antibodies to IL-18BPa to the stimulated THP-1 cultures resulted in increased levels of free IL-18, indicating a specific interaction between IL18 and IL-18BPa in this system. VIP (10−8M) inhibited both IL-18 and IL-18Bpa secretion by stimulated monocytes. We conclude that IL-18 and IL-18BPa secretion by monocytes is part of the immune response to Pg, and that VIP can inhibit this process.
Eugenol Inhibits K+ Currents in Trigeminal Ganglion Neurons
Authors: Li H.Y. , Park C.-K. , Jung S.J. , Choi S.-Y. , Lee S.J. , Park K. , Kim J.S. , Oh S.B.
Published: January 2009

Eugenol, a natural capsaicin congener, is widely used in dentistry. Eugenol inhibits voltage-activated Na+ and Ca2+ channels in a transient receptor potential vanilloid 1 (TRPV1)-independent manner. We hypothesized that eugenol also inhibits voltage-gated K+ currents, and investigated this in rat trigeminal ganglion neurons and in a heterologous system using whole-cell patch clamping. Eugenol inhibited voltage-gated K+ currents, and the inhibitory effects of eugenol were observed in both capsaicin-sensitive and capsaicin-insensitive neurons. Pre-treatment with capsazepine, a well-known antagonist of TRPV1, failed to block the inhibitory effects of eugenol on K+ currents, suggesting no involvement of TRPV1. Eugenol inhibited human Kv1.5 currents stably expressed in Ltk− cells, where TRPV1 is not endogenously expressed. We conclude that eugenol inhibits voltage-gated K+ currents in a TRPV1-independent manner. The inhibition of voltage-gated K+ currents is likely to contribute to the irritable action of eugenol. Abbreviations: human Kv1.5 channel, hKv1.5; transient receptor potential vanilloid 1, TRPV1.
Hypoxia Induces Expression and Activation of AMPK in Rat Dental Pulp Cells
Authors: Fukuyama Y. , Ohta K. , Okoshi R. , Suehara M. , Kizaki H. , Nakagawa K.
Published: January 2009

AMP-activated protein kinase (AMPK) is a stress-responsive enzyme involved in cell adaptation to an energy crisis. We hypothesized that hypoxia suppresses oxidative phosphorylation and ATP production, resulting in AMPK activation to protect cells. We investigated the effects of hypoxia on cell proliferation, the expression of AMPK and hypoxia-inducible factor 1α (HIF-1α), the activation of AMPK, and the relationship between AMPK and HIF-1α expression in rat dental pulp RPC-C2A cells. AMPK in the cells was composed of catalytic α1, and regulatory β1 and γ1 subunit isoforms. Cell proliferation was initially suppressed under hypoxia, but it increased thereafter, together with an increase in the expression of AMPK and HIF-1α, and the activation of AMPK. Down-regulation of AMPKα1 by siRNA inhibited cell proliferation under both normoxia and hypoxia, revealing that AMPK induction and activation were required for cell proliferation, although HIF-1α expression under hypoxia was not affected.
Peritubular Dentin Lacks Piezoelectricity
Authors: Habelitz S. , Rodriguez B.J. , Marshall S.J. , Marshall G.W. , Kalinin S.V. , Gruverman A.
Published: January 2009

Dentin is a mesenchymal tissue, and, as such, is based on a collagenous matrix that is reinforced by apatite mineral. Collagen fibrils show piezoelectricity, a phenomenon that is used by piezoresponse force microscopy (PFM) to obtain high-resolution images. We applied PFM to image human dentin with 10-nm resolution, and to test the hypothesis that zones of piezoactivity, indicating the presence of collagen fibrils, can be distinguished in dentin. Piezoelectricity was observed by PFM in the dentin intertubular matrix, while the peritubular dentin remained without response. High-resolution imaging of chemically treated intertubular dentin attributed the piezoelectric effect to individual collagen fibrils that differed in the signal strength, depending on the fibril orientation. This study supports the hypothesis that peritubular dentin is a non-collagenous tissue and is thus an exception among mineralized tissues that derive from the mesenchyme.
The Cranial Base in Craniofacial Development: a Gene Therapy Study
Authors: Kyrkanides S. , Kambylafkas P. , Miller J.H. , Tallents R.H. , Puzas J.E.
Published: January 2009

The etiology of midface retrusion remains largely unclear. We hypothesized that the cranial base synchondroses play a key role in the development of the craniofacial skeleton in the Sandhoff mouse model. We observed that developmental abnormalities of the cranial base synchondroses involving proliferative chondrocytes are important in craniofacial growth and development. Neonatal restitution of β-hexosaminidase in mutant mice by gene therapy successfully ameliorated the attendant skeletal defects and restored craniofacial morphology in vivo, suggesting this as a critical temporal window in craniofacial development. Analysis of our data implicates parathyroid-related peptide (PTHrP) and cyclo-oxygenase-2 (COX-2) as possible factors underlying the development of the aforementioned skeletal defects. Hence, timely restitution of a genetic deficiency or, alternatively, the restoration of PTHrP or cyclo-oxygenase activity by the administration of PTH and/or non-steroidal anti-inflammatory drugs or COX-2 selective inhibitors to affected individuals may prove beneficial in the management of midface retrusion.
Splicing Determines the Glycosylation State of Ameloblastin
Authors: Kobayashi K. , Yamakoshi Y. , Hu J.C.-C. , Gomi K. , Arai T. , Fukae M. , Krebsbach P.H. , Simmer J.P.
Published: January 2009

In developing porcine enamel, the space between enamel rods selectively binds lectins and ameloblastin (Ambn) N-terminal antibodies. We tested the hypothesis that ameloblastin N-terminal cleavage products are glycosylated. Assorted Ambn cleavage products showed positive lectin staining by peanut agglutinin (PNA), Maclura pomifera agglutinin (MPA), and Limulus polyphemus agglutinin (LPA), suggesting the presence of an O-linked glycosylation containing galactose (Gal), N-acetylgalactosamine (GalNAc), and sialic acid. Edman sequencing of the lectin-positive bands gave the Ambn N-terminal sequence: VPAFPRQPGTXGVASLXLE. The blank cycles for Pro11 and Ser17 confirmed that these residues are hydroxylated and phosphorylated, respectively. The O-glycosylation site was determined by Edman sequencing of pronase-digested Ambn, which gave HPPPLPXQPS, indicating that Ser86 is the site of the O-linked glycosylation. This modification is within the 15-amino-acid segment (73-YEYSLPVHPPPLPSQ-87) deleted by splicing in the mRNA encoding the 380-amino-acid Ambn isoform. We conclude that only the N-terminal Ambn products derived from the 395-Ambn isoform are glycosylated.
Targeting and Immobilization of Bioactive Peptides on Dentin Matrix
Authors: Song J.S. , Wlodarska A. , Ko H.J. , Grzesik W.J.
Published: January 2009

The regeneration of structurally/functionally competent tooth root cementum is a critical step for the successful restoration of periodontal attachment. In this study, we tested whether a poly-glutamic acid-rich domain and glutamine-containing transglutaminase substrate can be used to target biologically active peptides to the mineralized root matrix and to bind such peptides covalently to the organic matrix. As a biologically active model molecule, the integrin-binding motif, RGD, was used. The effects of immobilization of such synthetic peptides to the dentin matrix on cementoblastic adhesion in vitro and cementogenesis in vivo were studied. In vitro, cementoblastic adhesion improved significantly when the dentin surface contained covalently bound peptides. In vivo, this bound peptide significantly increased cementum formation compared with that attained in control conditions. Transglutaminase-catalyzed covalent binding of bioactive peptides targeted to mineralized collagenous dentin matrix via the poly-glutamate domain can be readily achieved. This approach offers potential for clinical use in periodontal regeneration.
PGE2Activates Cementoclastogenesis by CementoblastsviaEP4
Authors: Oka H. , Miyauchi M. , Sakamoto K. , Moriwaki S. , Niida S. , Noguchi K. , Somerman M.J. , Takata T.
Published: January 2009

Destruction of cementum and alveolar bone is the main causative event for the exfoliation of teeth as a consequence of periodontitis. Prostaglandin E2(PGE2) and PGE receptor subtypes (EPs) play an important role in modulating osteoblast-mediated osteoclastogenesis; however, no information is available on the role of PGE2and EPs in regulating cementoblast-mediated cementoclastogenesis. We hypothesized that the PGE2-EPs pathway also regulates cementoblasts’ ability to activate cementoclasts. For these studies, OCCM-30 cells (a mouse cementoblast cell line) were exposed to PGE2and specific EP agonists. PGE2(100 ng/mL) and EP4 agonist (1 μM) up-regulated RANKL and IL-6 mRNA levels, while they down-regulated OPG mRNA expression. The EP4 antagonist (1 μM) eliminated these effects of PGE2. PGE2treatment of co-cultures of OCCM-30 cells with bone marrow cells induced TRAP-positive cells via the EP4 pathway. These findings suggest that PGE2promotes cementoblast-mediated cementoclastogenesis by regulating the expression of RANKL and OPG via the EP4 pathway.
Defining Subphenotypes for Oral Clefts Based on Dental Development
Authors: Letra A. , Menezes R. , Granjeiro J.M. , Vieira A.R.
Published: January 2009

Individuals with clefts present considerably more dental anomalies than do individuals without clefts. We used dental development to subphenotype clefts with the goal of identifying cleft subgroups that could have specific genetic contributions. We examined 1000 individuals, 500 with clefts and 500 without. We used several clinical features, such as cleft completeness or incompleteness, laterality, and the presence of dental anomalies to assess each individual’s cleft status. We performed chi-square and Fisher’s exact tests to compare the frequencies of observed anomalies between individuals with and individuals without clefts, and among individuals with different cleft subphenotypes. Agenesis of the lateral incisor on the non-cleft side was the most remarkable observation, and may suggest that such cases could be considered incomplete forms of bilateral clefts of the lip.
Osteonecrosis of the Jaws and Bisphosphonate Therapy
Authors: Ruggiero S.L. , Drew S.J.
Published: January 2009

Bisphosphonates are a class of agents used to treat osteoporosis and malignant bone metastases. The efficacy of these agents in treating and preventing the significant skeletal complications associated with these conditions has had a major positive impact for patients and is responsible for their widespread use in medicine. Despite these benefits, osteonecrosis of the jaws has recently emerged as a significant complication in a subset of patients receiving these drugs. Based on a growing number of case reports and institutional reviews, bisphosphonate therapy may cause exposed and necrotic bone that is isolated to the jaw. This complication usually presents following simple dento-alveolar surgery, and can cause a significant adverse effect on the quality of life for most patients. The pathogenesis for this complication appears to be related to the profound inhibition of osteoclast function and bone remodeling.
Mechanism of Action, Pharmacokinetic and Pharmacodynamic Profile, and Clinical Applications of Nitrogen-containing Bisphosphonates
Authors: Kimmel D.B.
Published: January 2009

Nitrogen-containing bisphosphonates (nBPs) are bone-specific agents that inhibit farnesyl diphosphate synthase. nBPs’ strong affinity for bone, and not for other tissues, makes them potent inhibitors of bone resorption and bone remodeling activity, with limited potential for side-effects in non-skeletal tissues. Five nBPs are currently approved in the United States. The primary indications are for treatment of osteoporosis (alendronate, ibandronate, and risedronate) and treatment/prevention of skeletal-related events (SREs) in multiple myeloma and breast and prostate cancer patients (ibandronate, pamidronate, and zoledronic acid). nBPs are the most efficacious drugs available for these diseases, reducing osteoporotic fracture risk by 50–60% in persons with low bone mass or prior osteoporotic fracture, and SREs by one-third in cancer patients. The absorbed nBP dose for cancer patients is from seven to ten times that in osteoporosis patients. nBPs are unique in that they first exert profound pharmacodynamic effects long after their blood levels reach zero. Current pharmacokinetic studies indicate that approximately half of any nBP dose reaches the skeleton, with an early half-life of ten days, and a terminal half-life of about ten years. Practical study design limitations and theoretical considerations suggest that both the half-life and the amount of nBP retained in the skeletons of patients on long-term nBP therapy are substantially overestimated by extrapolation directly from current pharmacokinetic data. In fact, the amount of nBP being released from skeletal tissues of long-term-treated patients, particularly in osteoporosis patients, becomes insufficient to maintain full pharmacodynamic efficacy relatively soon after dosing is interrupted.
Sliding Contact Fatigue Damage in Layered Ceramic Structures
Authors: Kim J.-W. , Kim J.-H. , Thompson V.P. , Zhang Y.
Published: January 2009

Porcelain-veneered restorations often chip and fracture from repeated occlusal loading, making fatigue studies relevant. Most fatigue studies are limited to uni-axial loading without sliding motion. We hypothesized that bi-axial loading (contact-load-slide-liftoff, simulating a masticatory cycle), as compared with uni-axial loading, accelerates the fatigue of layered ceramics. Monolithic glass plates were epoxy-joined to polycarbonate substrates as a transparent model for an all-ceramic crown on dentin. Uni-and bi-axial cyclic contact was applied through a hard sphere in water, by means of a mouth-motion simulator apparatus. The uni-axial (contact-load-hold-liftoff) and traditional R-ratio fatigue (indenter never leaves the specimen surface) produced similar lifespans, while bi-axial fatigue was more severe. The accelerated crack growth rate in bi-axial fatigue is attributed to enhanced tensile stresses at the trailing edges of a moving indenter. Fracture mechanics descriptions for damage evolution in brittle materials loaded repeatedly with a sliding sphere are provided. Clinical relevance is addressed.
Rat Nerve Regeneration with the Use of a Polymeric Membrane Loaded with NGF
Authors: Savignat M. , De-Doncker L. , Vodouhe C. , Garza J.M. , Lavalle P. , Libersa P.
Published: January 2009

Exogenous neurotrophic factors, delivered by various systems, are used to improve nerve regeneration. This study tested the effectiveness of a polymeric membrane loaded with Nerve Growth Factor (NGF) on mental nerve regeneration after a crush injury in rats. We tested NGF application, known to play a role in afferent fiber repair in dental neurobiology, to see if it could improve the regeneration. Afferent neurogram recordings and histological analyses of the trigeminal ganglion neurons were performed. One month after the crush injury, early regeneration was observed independently of exogenous NGF. However, as compared with the activity level recorded before the injury, the afferent activity was reduced by 28.5% without NGF, and the mean number of labeled neurons decreased. With NGF, activity was increased by 30.8%, with no significant histological difference compared with animals without lesions. NGF application through a polymeric membrane can influence degenerative and/or regenerative processes after a crush injury.
Modulation of Epithelial Cell Fate of the Root in vitro
Authors: Tummers M. , Yamashiro T. , Thesleff I.
Published: January 2009

Mouse molars are normally not capable of continuous growth. We hypothesized that the mouse molar has intrinsic potential to maintain the epithelial stem cell niche and assessed this potential by growth in vitro. Although the tooth germs flattened considerably, they developed a mineralized crown and a root. However, histologically, the root surface was composed of 3 structurally different regions affecting the fate of the dental epithelium. The anterior and posterior aspects maintained the morphological and molecular characteristics of the cervical loop of a continuously growing incisor, with a continuous layer of ameloblasts. The epithelium making contact with the supporting filter resembled Hertwig’ss epithelial root sheath. The top of the cultured molar exposed to air lacked epithelium altogether. We conclude that the fate of the epithelium is regulated by external cues influenced by culture conditions, and that the molar has the intrinsic capacity to grow continuously.
The Role of Tumor Necrosis Factor Receptor Type 1 in Orthodontic Tooth Movement
Authors: Andrade I. , Silva T.A. , Silva G.A.B. , Teixeira A.L. , Teixeira M.M.
Published: January 2009

Orthodontic tooth movement is dependent on osteoclast activity. Tumor necrosis factor (TNF)-α plays an important role, directly or via chemokine release, in osteoclast recruitment and activation. This study aimed to investigate whether the TNF receptor type 1 (p55) influences these events and, consequently, orthodontic tooth movement. An orthodontic appliance was placed in wild-type mice (WT) and p55-deficient mice (p55−/−). Levels of TNF-α and 2 chemokines (MCP-1/CCL2, RANTES/CCL5) were evaluated in periodontal tissues. A significant increase in CCL2 and TNF-α was observed in both groups after 12 hrs of mechanical loading. However, CCL5 levels remained unchanged in p55−/− mice at this time-point. The number of TRAP-positive osteoclasts in p55−/− mice was significantly lower than that in WT mice. Also, there was a significantly smaller rate of tooth movement in p55−/− mice. Analysis of our data suggests that the TNFR-1 plays a significant role in orthodontic tooth movement that might be associated with changes in CCL5 levels.