bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Human Pulp Fibroblasts in Angiogenesis
Authors: Tran-Hung L. , Mathieu S. , About I.
Published: January 2009

After pulp amputation, complete pulp healing requires not only reparative dentin production but also fibroblast proliferation, nerve fiber growth, and neoangiogenesis. This study was designed to investigate the role of pulp fibroblasts in angiogenesis. Human pulp fibroblasts from third molars co-cultured with human umbilical vein endothelial cells induced the organization of endothelial cells and the formation of tubular structures corresponding to capillaries in vivo. The direct contact between both cells was not necessary to induce angiogenesis, and the observed effect was due to soluble factors. This was confirmed with neutralizing antibodies against FGF-2 and VEGF, which decreased the angiogenic effects of these soluble factors. Immunohistochemistry showed that both FGF-2 and VEGF were expressed in human dental pulp fibroblasts, and this expression increased after injury. These results suggest that the pulp fibroblasts secrete angiogenic factors, which are necessary for complete pulp healing, particularly at the pulp injury site.
PTCH Mutations in Sporadic and Gorlin-syndrome-related Odontogenic Keratocysts
Authors: Gu X.-M. , Zhao H.-S. , Sun L.-S. , Li T.-J.
Published: January 2009

Odontogenic keratocysts are relatively common lesions that may occur in isolation or in association with nevoid basal cell carcinoma syndrome (or Gorlin syndrome). The PTCH gene has been reported to be associated with Gorlin syndrome. We investigated 10 cases of non-syndromic keratocysts and two other cases associated with Gorlin syndrome, looking for PTCH mutations. Four novel and 1 known PTCH mutations were identified in five individual patients. Of the 5 mutations identified, 2 were germ-line mutations (2619C>A; 1338_1339insGCG) in 2 cysts associated with Gorlin syndrome, and 3 were somatic mutations (3124_3129dupGTGTGC; 1361_1364delGTCT; 3913G>T) in 3 non-syndromic cysts. This report describes PTCH mutations in both non-syndromic and Gorlin-syndrome-related odontogenic keratocysts in Chinese patients, and suggests that defects of PTCH are associated with the pathogenesis of syndromic as well as a subset of non-syndromic keratocysts.
The Role of Sucrose in Cariogenic Dental Biofilm Formation—New Insight
Authors: Leme A.F. Paes , Koo H. , Bellato C.M. , Bedi G. , Cury J.A.
Published: January 2009

Dental caries is a biofilm-dependent oral disease, and fermentable dietary carbohydrates are the key environmental factors involved in its initiation and development. However, among the carbohydrates, sucrose is considered the most cariogenic, because, in addition to being fermented by oral bacteria, it is a substrate for the synthesis of extracellular (EPS) and intracellular (IPS) polysaccharides. Therefore, while the low pH environment triggers the shift of the resident plaque microflora to a more cariogenic one, EPS promote changes in the composition of the biofilms’ matrix. Furthermore, it has recently been shown that the biofilm formed in the presence of sucrose presents low concentrations of Ca, Pi, and F, which are critical ions involved in de- and remineralization of enamel and dentin in the oral environment. Thus, the aim of this review is to explore the broad role of sucrose in the cariogenicity of biofilms, and to present a new insight into its influence on the pathogenesis of dental caries.
The Prx1 Homeobox Gene is Critical for Molar Tooth Morphogenesis
Authors: Mitchell J.M. , Hicklin D.M. , Doughty P.M. , Hicklin J.H. , Dickert J.W. , Tolbert S.M. , Peterkova R. , Kern M.J.
Published: January 2009

The paired-related homeobox genes, Prx1 and Prx2, encode transcription factors critical for orofacial development. Prx1 −/−/ Prx2 −/− neonates have mandibular hypoplasia and malformed mandibular incisors. Although the mandibular incisor phenotype has been briefly described (ten Berge et al., 1998 , 2001 ; Lu et al., 1999 ), very little is known about the role of Prx proteins during tooth morphogenesis. Since the posterior mandibular region was relatively normal, we examined molar tooth development in Prx1 −/−/ Prx2 −/− embryos to determine whether the tooth malformation is primary to the loss of Prx protein or secondary to defects in surrounding tissues. Three-dimensional (3D) morphological reconstructions demonstrated that Prx1 −/−/ Prx2 −/− embryos had molar malformations, including cuspal changes and ectopic epithelial projections. Although we demonstrate that Prx1 protein is expressed only mesenchymally, 3D reconstructions showed important morphological defects in epithelial tissues at the cap and bell stages. Analysis of these data suggests that the Prx homeoproteins are critical for mesenchymal-epithelial signaling during tooth morphogenesis.
Origin, Splicing, and Expression of Rodent Amelogenin Exon 8
Authors: Bartlett J.D. , Ball R. L. , Kawai T. , Tye C.E. , Tsuchiya M. , Simmer J.P.
Published: January 2009

Amelogenin RNA transcripts undergo extensive alternative splicing, and MMP-20 processes the isoforms following their secretion. Since amelogenins have been ascribed cell-signaling activities, we asked if a lack of proteolytic processing by MMP-20 affects amelogenin signaling and consequently alters amelogenin splice site selection. RT-PCR analyses of amelogenin mRNA between control and Mmp20 − /−mice revealed no differences in the splicing pattern. We characterized 3 previously unidentified amelogenin alternatively spliced transcripts and demonstrated that exon-8-encoded amelogenin isoforms are processed by MMP-20. Transcripts with exon 8 were expressed approximately five-fold less than those with exon 7. Analyses of the mouse and rat amelogenin gene structures confirmed that exon 8 arose in a duplication of exons 4 through 5, with translocation of the copy downstream of exon 7. No downstream genomic sequences homologous to exons 4–5 were present in the bovine or human amelogenin genes, suggesting that this translocation occurred only in rodents.
Eugenol Inhibits Sodium Currents in Dental Afferent Neurons
Authors: Park C.-K. , Li H.Y. , Yeon K.-Y. , Jung S.J. , Choi S.-Y. , Lee S.J. , Lee S. , Park K. , Kim J.S. , Oh S.B.
Published: January 2009

Although eugenol is widely used in dentistry, little is known about the molecular mechanisms responsible for its anesthetic properties. In addition to calcium channels, recently demonstrated by our group, there could be another molecular target for eugenol. Using a whole-cell patch-clamp technique, we investigated the effect of eugenol on voltage-gated sodium channel currents ( INa) in rat dental primary afferent neurons identified by retrograde labeling with a fluorescent dye in maxillary molars. Eugenol inhibited action potentials and INain both capsaicin-sensitive and capsaicin-insensitive neurons. The pre-treatment with capsazepine, a competitive antagonist of transient receptor potential vanilloid 1 (TRPV1), failed to block the inhibitory effect of eugenol on INa, suggesting no involvement of TRPV1. Two types of INa, tetrodotoxin (TTX)-resistant and TTX-sensitive INa, were inhibited by eugenol. Our results demonstrated that eugenol inhibits INain a TRPV1-independent manner. We suggest that INainhibition by eugenol contributes to its analgesic effect.
Laser-Fluoride Effect on Root Demineralization
Authors: Gao X.-L. , Pan J.-S. , Hsu C.-Y.
Published: January 2009

Although the individual cariostatic effects of laser and fluoride have been shown, the combined effect of CO2 laser and fluoride on root demineralization remains uncertain and was the main aim of this study. By using a pH-cycling system and Polarized Light Microscopy, we demonstrated the synergistic effect of fluoride combined with CO2 laser treatment on reducing root demineralization. The mean lesion depths (in μm) for each group were 160 ± 14 (Control), 113 ± 8 (Laser treatment alone), 111 ± 6 (Fluoride treatment alone), and 25 ± 7 (Fluoride followed by laser treatment). A significant laser-enhanced fluoride uptake, characterized by the ToF-SIMS analysis, was revealed by the 37% and 400% increments in loosely and firmly bound fluorides (both p < 0.002) in laser-irradiated areas, compared with the non-irradiated controls. In conclusion, there is a significant synergistic effect of combined CO2 laser and fluoride treatment on the inhibition of root demineralization, possibly due to laser-enhanced fluoride uptake in the root.
Chemical Interaction of Phosphoric Acid Ester with Hydroxyapatite
Authors: Fukegawa D. , Hayakawa S. , Yoshida Y. , Suzuki K. , Osaka A. , Van Meerbeek B.
Published: January 2009

Among functional monomers used in contemporary dental adhesives, 10-methacryloyloxydecyl dihydrogen phosphate (MDP) has been found to interact chemically with hydroxyapatite (HAp) most intensively and stably. This effect was thought to be the basis of the superior bonding effectiveness of MDP-based self-etch adhesives to enamel/dentin. To elucidate fully the chemical interaction and reactivity of MDP with HAp, we used 31P CP-MAS NMR spectroscopy and powder x-ray diffraction. In an aqueous ethanol solution, Ca ions were leached from HAp to form, at short term, a MDP-calcium salt (CaMHP2) layered structure on the HAp surface. When MDP was allowed to interact for longer time (< 24 hrs), CaHPO4·2H2O precipitated on top of this MDP-calcium salt layered structure. In conclusion, the intense chemical interaction of MDP with HAp must be ascribed to superficial dissolution of HAp induced by the MDP adsorption and subsequent deposition of MDP-calcium salt with a solubility lower than that of CaHPO4·2H2O.
Emerging Mechanisms of Immunosuppression in Oral Cancers
Authors: Jewett A. , Head C. , Cacalano N.A.
Published: January 2009

Mounting effective anti-tumor immune responses against tumors by both the innate and adaptive immune effectors is important for the clearance of tumors. However, accumulated evidence indicates that immune responses that should otherwise suppress or eliminate transformed cells are themselves suppressed by the function of tumor cells in a variety of cancer patients, including those with oral cancers. Signaling abnormalities, spontaneous apoptosis, and reduced proliferation and function of circulating natural killer cells (NK), T-cells, dendritic cells (DC), and tumor-infiltrating lymphocytes (TILs) have been documented previously in oral cancer patients. Several mechanisms have been proposed for the functional deficiencies of tumor-associated immune cells in oral cancer patients. Both soluble factors and contact-mediated immunosuppression by the tumor cells have been implicated in the inhibition of immune cell function and the progression of tumors. More recently, elevated levels and function of key transcription factors in tumor cells, particularly NFκB and STAT3, have been shown to mediate immune suppression in the tumor microenvironment. This review will focus on these emerging mechanisms of immunosuppression in oral cancers.
Tissue Inhibitors of Metalloproteinases (TIMPs): Their Biological Functions and Involvement in Oral Disease
Authors: Verstappen J. , Von den Hoff J.W.
Published: January 2009

Several families of enzymes are responsible for the degradation of extracellular matrix (ECM) proteins during the remodeling of tissues. An important family of such enzymes is that of the matrix metalloproteinases (MMPs). To control MMP-mediated ECM breakdown, tissue inhibitors of metalloproteinases (TIMPs) are able to inhibit MMP activity. A disturbed balance of MMPs and TIMPs is found in various pathologic conditions, such as cancer, rheumatoid arthritis, and periodontitis. The role of MMPs in pathology has been extensively described in the literature. The main focus of this review lies in the biological functions of TIMPs and their occurrence in disease, especially in the head and neck area. Their biological functions and their role in diseases like oral cancers and periodontitis, and in the development of cleft palate, will be discussed. Finally, the diagnostic and therapeutical opportunities of TIMPs will be evaluated.
Duty Time of Rabbit Jaw Muscles Varies with the Number of Activity Bursts
Authors: Grünheid T. , Langenbach G.E.J. , Zentner A. , Van Eijden T.M.G.J.
Published: January 2009

The relative duration of muscle activity during a specified period (duty time) varies depending on activity level and time of the day. Since both the number and the length of activity bursts contribute to the duty time, it was hypothesized that these variables would show intra-day variations similar to those of the duty time. To test this, we determined duty times, burst numbers, and burst lengths per hour, in relation to multiple activity levels, in a 24-hour period of concurrent radio-telemetric long-term electromyograms of various rabbit jaw muscles. The marked intra-day variation of the burst number resembled that of the duty time in all muscles, and was in contrast to the relatively invariable mean burst length. Furthermore, the duty times were more highly correlated with the number than with the length of bursts at all activity levels. Thus, the variation of the duty time in rabbit jaw muscles is caused mainly by changes in burst numbers.
Anti-P. gingivalis Response Correlates with Atherosclerosis
Authors: Ford P.J. , Gemmell E. , Timms P. , Chan A. , Preston F.M. , Seymour G.J.
Published: January 2009

Significant associations between atherosclerosis and both Porphyromonas gingivalis, a major periodontopathogen, and the respiratory pathogen, Chlamydia pneumoniae, have been shown. Many individuals with evidence of atherosclerosis demonstrate seropositivity to these pathogens. The aim of the present study was to examine the atherogenic effect of repeated immunizations with either or both of these agents, and to determine if molecular mimicry of bacterial heat-shock protein (HSP), termed GroEL, and host (h) HSP60 was involved. Atherogenesis was examined in apolipoprotein-E-deficient (−/−) mice following intraperitoneal immunizations with P. gingivalis, C. pneumoniae, P. gingivalis, and C. pneumoniae or vehicle. Lesion area in the proximal aorta and levels of serum antibodies to P. gingivalis, C. pneumoniae, and GroEL were measured. The increased pathogen burden of P. gingivalis, but not of C. pneumoniae, enhanced atherosclerosis. hHSP60 was detected in lesions, and in P. gingivalis-immunized mice, lesion development was correlated with anti-GroEL antibody levels, supporting the involvement of molecular mimicry between GroEL and hHSP60.
Smart Bracket for Multi-dimensional Force and Moment Measurement
Authors: Lapatki B.G. , Bartholomeyczik J. , Ruther P. , Jonas I.E. , Paul O.
Published: January 2009

Atraumatic, well-directed, and efficient tooth movement is interrelated with the therapeutic application of adequately dimensioned forces and moments in all three dimensions. The lack of appropriate monitoring tools inspired the development of an orthodontic bracket with an integrated microelectronic chip equipped with multiple piezoresistive stress sensors. Such a ‘smart bracket’ was constructed (scale of 2.5:1) and calibrated. To evaluate how accurately the integrated sensor system allowed for the quantitative determination of three-dimensional force-moment systems externally applied to the bracket, we exerted 396 different force-moment combinations with dimensions within usual therapeutic ranges (± 1.5 N and ± 15 Nmm). Comparison between the externally applied force-moment components and those reconstructed on the basis of the stress sensor signals revealed very good agreement, with standard deviations in the differences of 0.037 N and 0.985 Nmm, respectively. We conclude that our methodological approach is generally suitable for monitoring the relatively low forces and moments exerted on individual teeth with fixed orthodontic appliances.
Nitric Oxide in Pulp Cell Growth, Differentiation, and Mineralization
Authors: Yasuhara R. , Suzawa T. , Miyamoto Y. , Wang X. , Takami M. , Yamada A. , Kamijo R.
Published: January 2009

Dental preparation sometimes causes transient congestion, edema, and necrosis of the pulp. We hypothesized that nitric oxide (NO) is involved in the pathophysiological changes in pulp after preparation. The mRNA and protein expression of the inducible isoform of NO synthase (iNOS) was examined in murine pulp after dental preparation. The effects of NO on the proliferation, mineralization, and apoptosis of pulp cells were also studied in vitro. We found that not only iNOS, but also mRNAs for alkaline phosphatase and plasma membrane glycoprotein-1, were expressed in the pulp after preparation. NOC-18, an NO donor, suppressed the proliferation of pulp cells without inducing cell death, whereas it promoted the mineralization of cells cultured in the presence of β-glycerophosphate, ascorbic acid, dexamethasone, and KH2PO4. Under these conditions, NOC-18 induced the apoptosis of pulp cells. These results suggest that NO regulates the growth, apoptosis, and mineralization of pulp cells.
Bacterial Infection Promotes DNA Hypermethylation
Authors: Bobetsis Y.A. , Barros S.P. , Lin D.M. , Weidman J.R. , Dolinoy D.C. , Jirtle R.L. , Boggess K.A. , Beck J.D. , Offenbacher S.
Published: January 2009

Maternal oral infection, caused by bacteria such as C. rectus or P. gingivalis, has been implicated as a potential source of placental and fetal infection and inflammatory challenge, which increases the relative risk for pre-term delivery and growth restriction. Intra-uterine growth restriction has also been reported in various animal models infected with oral organisms. Analyzing placental tissues of infected growth-restricted mice, we found down-regulation of the imprinted Igf2 gene. Epigenetic modification of imprinted genes via changes in DNA methylation plays a critical role in fetal growth and development programming. Here, we assessed whether C. rectus infection mediates changes in the murine placenta Igf2 methylation patterns. We found that infection induced hypermethylation in the promoter region-P0 of the Igf2 gene. This novel finding, correlating infection with epigenetic alterations, provides a mechanism linking environmental signals to placental phenotype, with consequences for development.
Micromolar Fluoride Alters Ameloblast Lineage Cells in vitro
Authors: Yan Q. , Zhang Y. , Li W. , DenBesten P.K.
Published: January 2009

Fluorosed enamel is caused by exposure to fluoride during tooth formation. The objective of this study was to determine whether epithelial ameloblast-lineage cells, derived from the human enamel organ, are directly affected by micromolar concentrations of fluoride. Cells were cultured in the presence of fluoride, and proliferation was measured by BrdU incorporation. The effect of 0, 10, or 20 μM fluoride on apoptosis was determined by the flow cytometry apoptotic index. The effects of fluoride on gene expression were investigated by SuperArray microarray analysis and real-time PCR. Fluoride had a biphasic effect on cell proliferation, with enhanced proliferation at 16 μM, and reduced proliferation at greater than 1 mM F. Flow cytometry showed that both 10 μM and 20 μM NaF significantly increased the apoptotic index of ameloblast-lineage cells. There was no general effect of fluoride on gene expression. These results indicate multiple effects of micromolar fluoride on ameloblast-lineage cells.
Tobacco Use and Incidence of Tooth Loss among US Male Health Professionals
Authors: Dietrich T. , Maserejian N.N. , Joshipura K.J. , Krall E.A. , Garcia R.I.
Published: January 2009

Data on the dose-dependent effects of smoking and smoking cessation on tooth loss are scarce. We hypothesized that smoking has both dose- and time-dependent effects on tooth loss incidence. We used longitudinal data on tobacco use and incident tooth loss in 43,112 male health professionals, between 1986 and 2002. In multivariate Cox models, current smokers of 5 to 14 and 45+ cigarettes daily had a two-fold (HR, 1.94; 95% CI, 1.72, 2.18) and three-fold (HR, 3.05; 95% CI, 2.38, 3.90) higher risk of tooth loss, respectively, compared with never-smokers. Risk decreased with increasing time since cessation, but remained elevated by 20% (95% CI, 16%, 25%) for men who had quit 10+ years before. Current pipe/cigar smokers had a 20% (95% CI, 1.11, 1.30) increased risk of tooth loss compared with never- and former smokers of pipes/cigars.
Hereditary Dentin Defects
Authors: Kim J.-W. , Simmer J.P.
Published: January 2009

By the Shields classification, articulated over 30 years ago, inherited dentin defects are divided into 5 types: 3 types of dentinogenesis imperfecta (DGI), and 2 types of dentin dysplasia (DD). DGI type I is osteogenesis imperfecta (OI) with DGI. OI with DGI is caused, in most cases, by mutations in the 2 genes encoding type I collagen. Many genes are required to generate the enzymes that catalyze collagen’s diverse post-translational modifications and its assembly into fibers, fibrils, bundles, and networks. Rare inherited diseases of bone are caused by defects in these genes, and some are occasionally found to include DGI as a feature. Appreciation of the complicated genetic etiology of DGI associated with bony defects splintered the DGI type I description into a multitude of more precisely defined entities, all with their own designations. In contrast, DD-II, DGI-II, and DGI-III, each with its own pattern of inherited defects limited to the dentition, have been found to be caused by various defects in DSPP (dentin sialophosphoprotein), a gene encoding the major non-collagenous proteins of dentin. Only DD-I, an exceedingly rare condition featuring short, blunt roots with obliterated pulp chambers, remains untouched by the revolution in genetics, and its etiology is still a mystery. A major surprise in the characterization of genes underlying inherited dentin defects is the apparent lack of roles played by the genes encoding the less-abundant non-collagenous proteins in dentin, such as dentin matrix protein 1 ( DMP1), integrin-binding sialoprotein ( IBSP), matrix extracellular phosphoglycoprotein ( MEPE), and secreted phosphoprotein-1, or osteopontin ( SPP1, OPN). This review discusses the development of the dentin extracellular matrix in the context of its evolution, and discusses the phenotypes and clinical classifications of isolated hereditary defects of tooth dentin in the context of recent genetic data respecting their genetic etiologies.
Effectiveness of Fluoride in Preventing Caries in Adults
Authors: Griffin S.O. , Regnier E. , Griffin P.M. , Huntley V.
Published: January 2009

To date, no systematic reviews have found fluoride to be effective in preventing dental caries in adults. The objective of this meta-analysis was to examine the effectiveness of self- and professionally applied fluoride and water fluoridation among adults. We used a random-effects model to estimate the effect size of fluoride (absolute difference in annual caries increment or relative risk ratio) for all adults aged 20+ years and for adults aged 40+ years. Twenty studies were included in the final body of evidence. Among studies published after/during 1980, any fluoride (self- and professionally applied or water fluoridation) annually averted 0.29 (95%CI: 0.16–0.42) carious coronal and 0.22 (95%CI: 0.08–0.37) carious root surfaces. The prevented fraction for water fluoridation was 27% (95%CI: 19%–34%). These findings suggest that fluoride prevents caries among adults of all ages.
Sequence of Oral Bacterial Co-adhesion and Non-contact Brushing
Authors: van der Mei H.C. , Rustema-Abbing M. , Bruinsma G.M. , Gottenbos B. , Busscher H.J.
Published: January 2009

Non-contact plaque removal offers advantages in interproximal spaces, fissures, and pockets. It requires the generation of strong fluid flows and the inclusion of air bubbles to become effective. A pair of co-adhering streptococci and actinomyces has been used previously to demonstrate non-contact removal by sonic brushing. Here we determined the influence of the sequence of co-adhesion of streptococci and actinomyces on non-contact removal from a salivary pellicle by rotary and sonic brushing. After bacterial adhesion, pellicles were brushed in a wet and immersed state, with a distance up to 4 mm to the bristle tips. Bacteria adhering to pellicles from the sequence streptococci followed by actinomyces appeared more difficult to remove and left more large co-aggregates than from the sequence actinomyces followed by streptococci. At contact, rotary and sonic brushing performed equally well in bacterial removal, while at 4 mm, both had lost some efficacy.
Arg-gingipain A DNA Vaccine Prevents Alveolar Bone Loss in Mice
Authors: Miyachi K. , Ishihara K. , Kimizuka R. , Okuda K.
Published: January 2009

One major pathogenic factor of Porphyromonas gingivalis is Arg-gingipain (Rgp), an arginine-specific cysteine proteinase. To clarify the effect of rgpA DNA vaccine, we immunized BALB/c mice via the abdomen with a Gene Gun or via the nasal cavity weekly for 6 weeks. After immunization, the mice were challenged orally with P. gingivalis. Immunization elicited IgG responses against P. gingivalis in both groups. Nasal immunization also induced sIgA against P. gingivalis, although Gene Gun immunization did not. Reduction of alveolar bone loss was observed in both groups at 42 days following initial infection. This effect was more pronounced in the intranasal immunization group than in the Gene Gun group. The results of this study suggest that immunization with rgpA DNA vaccine via the nasal cavity is an effective method for preventing alveolar bone loss incurred by infection with P. gingivalis.
Effect of Aqueous Ozone on the NF-κB System
Authors: Huth K.C. , Saugel B. , Jakob F.M. , Cappello C. , Quirling M. , Paschos E. , Ern K. , Hickel R. , Brand K.
Published: January 2009

Ozone has been proposed as an alternative oral antiseptic in dentistry, due to its antimicrobial power reported for gaseous and aqueous forms, the latter showing a high biocompatibility with mammalian cells. New therapeutic strategies for the treatment of periodontal disease and apical periodontitis should consider not only antibacterial effects, but also their influence on the host immune response. Therefore, our aim was to investigate the effect of aqueous ozone on the NF-κB system, a paradigm for inflammation-associated signaling/transcription. We showed that NF-κB activity in oral cells stimulated with TNF, and in periodontal ligament tissue from root surfaces of periodontally damaged teeth, was inhibited following incubation with ozonized medium. Under this treatment, IκBα proteolysis, cytokine expression, and κB-dependent transcription were prevented. Specific ozonized amino acids were shown to represent major inhibitory components of ozonized medium. In summary, our study establishes a condition under which aqueous ozone exerts inhibitory effects on the NF-κB system, suggesting that it has an anti-inflammatory capacity.
Effects of COX-2 Inhibitor in Temporomandibular Joint Acute Inflammation
Authors: Schütz T.C.B. , Andersen M.L. , Tufik S.
Published: January 2009

Since it is recognized that cyclo-oxygenase-2 mediates nociception and the sleep-wake cycle as well, and that acute inflammation of the temporomandibular joint (TMJ) results in sleep disturbances, we hypothesized that cyclo-oxygenase-2 inhibitor would restore the sleep pattern in this inflammatory rat model. First, sleep was monitored after the injection of Freund’s adjuvant (FA group) or saline (SHAM group) into the rats’ temporomandibular joint. Second, etoricoxib was co-administered in these groups. The Freund’s adjuvant group showed a reduction in sleep efficiency, in rapid eye movement (REM), and in non-REM sleep, and an increase in sleep and REM sleep latency when compared with the SHAM group, while etoricoxib substantially increased sleep quality in the Freund’s adjuvant group. These parameters returned progressively to those found in the SHAM group. Etoricoxib improved the sleep parameters, suggesting the involvement of the cyclo-oxygenase-2 enzyme in acute inflammation of the TMJ, specifically in REM sleep.
Orofacial Pain in Cancer: Part I—Mechanisms
Authors: Benoliel R. , Epstein J. , Eliav E. , Jurevic R. , Elad S.
Published: January 2009

The mechanisms involved, and possible treatment targets, in orofacial pain due to cancer are poorly understood. The aim of the first of this two-part series is to review the involved pathophysiological mechanisms and explore their possible roles in the orofacial region. However, there is a lack of relevant research in the trigeminal region, and we have therefore applied data accumulated from experiments on cancer pain mechanisms in rodent spinal models. In the second part, we review the clinical presentation of cancer-associated orofacial pain at various stages: initial diagnosis, during therapy (chemo-, radiotherapy, surgery), and in the post-therapy period. In the present article, we provide a brief outline of trigeminal functional neuro-anatomy and pain-modulatory pathways. Tissue destruction by invasive tumors (or metastases) induces inflammation and nerve damage, with attendant acute pain. In some cases, chronic pain, involving inflammatory and neuropathic mechanisms, may ensue. Distant, painful effects of tumors include paraneoplastic neuropathic syndromes and effects secondary to the release of factors by the tumor (growth factors, cytokines, and enzymes). Additionally, pain is frequent in cancer management protocols (surgery, chemotherapy, and radiotherapy). Understanding the mechanisms involved in cancer-related orofacial pain will enhance patient management.
Tubular Occlusion Optimizes Bonding of Hydrophobic Resins to Dentin
Authors: Sadek F.T. , Pashley D.H. , Ferrari M. , Tay F.R.
Published: January 2009

Although hydrophobic resins may be bonded to acid-etched dentin with an ethanol wet-bonding technique, the protocol is sensitive to moisture contamination when bonding is performed in deep dentin. This study tested the hypothesis that the use of oxalate or poly(glutamic) acid-modified, diluted ceramicrete (PADC) for dentinal tubule occlusion prevents fluid contamination and improves the bonding of an experimental hydrophobic adhesive to acid-etched, ethanol-dehydrated dentin. Mid-coronal and deep acid-etched moist dentin pre-treated with oxalate or PADC was dehydrated by ethanol wet-bonding and infiltrated with the experimental three-step etch-and-rinse hydrophobic adhesive under simulated pulpal pressure. Tensile bond strengths to deep dentin without pre-treatment were severely compromised. Conversely, oxalate and PADC pre-treatments reduced dentin permeability, prevented water contamination, and improved bond strengths. Minimal nanoleakage was identified within hybrid layers created in the oxalate- and PADC-pre-treated deep dentin. The use of tubular occluding agents optimized bonding of hydrophobic resins to dentin.
In vivo Preservation of the Hybrid Layer by Chlorhexidine
Authors: Carrilho M.R.O. , Geraldeli S. , Tay F. , de Goes M.F. , Carvalho R.M. , Tjäderhane L. , Reis A.F. , Hebling J. , Mazzoni A. , Breschi L. , Pashley D.
Published: January 2009

Host-derived proteases have been reported to degrade the collagen matrix of incompletely-resin-infiltrated dentin. This study tested the hypothesis that interfacial degradation of resin-dentin bonds may be prevented or delayed by the application of chlorhexidine (CHX), a matrix metalloproteinase inhibitor, to dentin after phosphoric acid-etching. Contralateral pairs of resin-bonded Class I restorations in non-carious third molars were kept under intra-oral function for 14 months. Preservation of resin-dentin bonds was assessed by microtensile bond strength tests and TEM examination. In vivo bond strength remained stable in the CHX-treated specimens, while bond strength decreased significantly in control teeth. Resin-infiltrated dentin in CHX-treated specimens exhibited normal structural integrity of the collagen network. Conversely, progressive disintegration of the fibrillar network was identified in control specimens. Auto-degradation of collagen matrices can occur in resin-infiltrated dentin, but may be prevented by the application of a synthetic protease inhibitor, such as chlorhexidine.
Genetic Changes in Sporadic Keratocystic Odontogenic Tumors (Odontogenic Keratocysts)
Authors: Heikinheimo K. , Jee K.J. , Morgan P.R. , Nagy B. , Knuutila S. , Leivo I.
Published: January 2009

Little is known about the genetic background of keratocystic odontogenic tumors (KCOT, odontogenic keratocysts). Our aim was to characterize genomic aberrations in sporadic KCOT using cDNA-expression arrays and array-comparative genomic hybridization. For cDNA-expression arrays, 10 KCOT specimens and 20 fetal tooth germs were studied. Quantitative real-time reverse-transcription/polymerase chain-reaction and immunohistochemical studies were also undertaken. Several genes were over-expressed in 12q13, including cytokeratin 6B ( KRT6B) (≈ 10-fold), epidermal growth factor receptor ERBB3 (~ 4.7-fold), and glioma-associated oncogene homologue 1 ( GLI1) (~ 5- to 12-fold). One amplicon (~ 0.7 Mega base pairs [Mbp]), covering several genes involved in the regulation of cell growth, was found in 12q13.2. Deletions were found in 3q13.1, 5p14.3, and 7q31.3, including the cell-adhesion-related gene cadherin 18 ( CDH18) and leukocyte cell adhesion molecule ( ALCAM, MEMD). Over-expressed and amplified genes in 12q13, also reported in several other tumors and cell lines, may contribute to the persistent growth characteristics of KCOT.
Bacteria Interfere with A. actinomycetemcomitans Colonization
Authors: Teughels W. , Kinder Haake S. , Sliepen I. , Pauwels M. , Van Eldere J. , Cassiman J.-J. , Quirynen M.
Published: January 2009

It is known that beneficial bacteria can suppress the emergence of pathogenic bacteria, particularly in the gastrointestinal tract. This study examined the potential for a similar suppression of Aggregatibacter (formerly Actinobacillus) actinomycetemcomitans colonization of epithelial cells, due to its potential relevance in periodontal diseases. Seven presumed beneficial bacteria were examined for their ability to interfere, exclude, or displace A. actinomycetemcomitans from epithelial cells in vitro. Streptococcus sanguinis, Streptococcus mitis, and Streptococcus salivarius showed prominent inhibitory effects on either A. actinomycetemcomitans recovery or colonization. These results confirmed the hypothesis that bacterial interactions interfere with A. actinomycetemcomitans colonization of epithelial cells in vitro, and demonstrated the potential beneficial effects of S. mitis, S. salivarius, and S. sanguinis.
Testing a Conceptual Model of Oral Health: a Structural Equation Modeling Approach
Authors: Baker S.R.
Published: January 2009

Locker’s (1988) multidimensional model of oral health provides a scientific model for the understanding of oral disease and its consequences. To date, there have been no studies that have explicitly tested the model with empirical evidence. This study aimed to: first, test the model in a general population sample using data from the UK adult dental health survey (N = 5268); and, second, to cross-validate these results in two different and diverse samples—edentulous elders (N = 133) and a clinical sample of xerostomia patients (N = 85). Structural equation modeling indicated support for the model as applied to each of the samples. All of the direct pathways hypothesized by the model were significant, in addition to several indirect or mediated pathways between key variables. Further conceptual development of the model is discussed, particularly the role of individual difference factors, and theoretical and methodological issues in oral-health-related quality-of-life research are highlighted. Abbreviations: oral health quality of life (OHQoL); structural equation modeling (SEM); Adult Dental Health Survey (ADH survey); Oral health Impact Profile-short form (OHIP14).
Neutrophil Hyper-responsiveness in Periodontitis
Authors: Matthews J.B. , Wright H.J. , Roberts A. , Ling-Mountford N. , Cooper P.R. , Chapple I.L.C.
Published: January 2009

Peripheral neutrophil hyper-responsiveness in chronic periodontitis leads to excessive reactive oxygen species (ROS) production. We aimed to determine whether neutrophil hyper-responsiveness was constitutive or reactive, and to discover the effect of non-surgical therapy. Peripheral blood neutrophils from patients (n = 19), before and 3 months after therapy, and matched control individuals were Fcγ-receptor-stimulated with/without priming with P. gingivalis and F. nucleatum. Total and extracellular ROS were determined by luminol/isoluminol chemiluminescence. The high total ROS generation of patients’ neutrophils compared with that of control individuals ( P = 0.016) continued at a reduced level post-therapy ( P = 0.059). Reduced activity post-therapy was also seen with priming. Unstimulated total ROS levels did not differ between patients and control individuals before or after therapy. However, the high unstimulated, extracellular ROS production by patients’ neutrophils compared with control individuals ( P < 0.05) continued post-therapy and was unaffected by priming. Therapy reduced Fcγ-receptor-stimulated total ROS production, but not unstimulated extracellular radical release, suggesting that constitutive and reactive mechanisms underlie neutrophil hyper-responsiveness.
Breaking Biological Barriers with a Toothbrush
Authors: Amano K. , Miyake K. , Borke J.L. , McNeil P.L.
Published: January 2009

Toothbrushing exposes epithelia and other tissues of the oral cavity to mechanical stress. Here, we investigated whether brushing induces cell wounding—plasma membrane disruption—in epithelial and other cell types in the oral cavity. Brushing of the gingivae and tongues of rats resulted in a striking increase in the number of cells positive for a marker of disruption injury. These cells included those in all strata of the gingival epithelium, and in the skeletal muscle of the tongue. Additionally, we found that brushing resulted in an increase in c-fos expression by junctional epithelial and skeletal muscle cells. Epithelial barrier function, however, was not overtly affected by brushing, despite the observed individual injuries to cells. We concluded that brushing disrupts cell plasma membrane barriers in the oral cavity and activates gene expression events that may lead to local adaptive changes in tissue architecture beneficial to gingival health.
Effects of Compressive Loading on Human Synovium-derived Cells
Authors: Muroi Y. , Kakudo K. , Nakata K.
Published: January 2009

Compressive stress may be involved in temporomandibular joint (TMJ) synovitis, but its mechanism has not been fully elucidated. We hypothesized that mechanical stress to the synovial cells of the TMJ potentially causes degenerative changes in temporomandibular joint disease. We examined the effect of cyclic compressive loading on three-dimensionally engineered constructs using human TMJ synovium-derived cells in vitro. Human TMJ synovium-derived cells were cultured onto collagen scaffolds, resulting in three-dimensional constructs. Cyclic compression loading was applied to the constructs by means of a custom-designed apparatus. DNA amount, apoptotic cells, and mRNA levels for inflammatory cytokines were analyzed. The protein expression and activity of MMPs were examined. DNA amount or apoptotic cell number was unchanged by loading. MMP-2, -3, and IL-8 mRNA expression was up-regulated by the compression, and both MMP-1 and -3 protein expression and MMP-2 activity were detected. Thus, compression of human TMJ synovium-derived cells appears to modulate inflammatory cytokines.
Cholinoreceptor Autoantibodies in Sjögren Syndrome
Authors: Reina S. , Orman B. , Anaya J.M. , Sterin-Borda L. , Borda E.
Published: January 2009

Previous studies have demonstrated that antibodies against cholinoreceptors of exocrine glands correlate with dry mouth in persons with primary Sjögren syndrome (pSS). The aim of the present investigation was to establish if serum IgG antibodies (pSS IgG) were able to interact with cholinoreceptors in rat submandibular gland-dependent stimulation of cyclooxygenase 2 (COX-2) mRNA expression and PGE2 production. Our findings indicated that pSS IgG-stimulating M3, M4, and M1 cholinoreceptors exerted an increase in COX-2 mRNA without affecting COX-1 mRNA expression and increased PGE2 production. Inhibitors of phospholipase A2, COX- s, L-type calcium channel currents, and Ca2+-ATPase from sarcoplasmic reticulum prevented the pSS IgG effect on PGE2 production. An ionophore of calcium mimicked pSS IgG action, suggesting a crucial role of calcium homeostasis in the cholinoreceptor-stimulated increase in PGE2 production. Moreover, the amounts of PGE2 in saliva and in sera from persons with pSS were significantly higher than in pre- or post-menopausal women. These findings illustrate the importance of autoantibodies to cholinoreceptors in the generation of chronic inflammation of target tissues in SS.
Dentin in Severe Fluorosis: a Quantitative Histochemical Study
Authors: Rojas-Sánchez F. , Alaminos M. , Campos A. , Rivera H. , Sánchez-Quevedo M.C.
Published: January 2009

Dentin responds to different alterations in the enamel with hypermineralization, and is a biomarker of fluoride exposure. We hypothesized that severe fluorosis would lead to hypermineralization of the dentin when the enamel was severely affected. We used scanning electron microscopy and quantitative electron-probe microanalysis to compare dentin and enamel from healthy and fluorotic teeth. The dentin in fluorotic teeth was characterized by a highly mineralized sclerotic pattern, in comparison with control teeth (p < 0.001) and fluorotic enamel lesions (p < 0.001). Enamel near the lesions showed hypercalcification in comparison with dentin (p < 0.001). In response to the effects of severe fluorosis in the enamel, the dentin showed hypermineralization, as found in other enamel disorders. The hypermineralization response of the dentin in our samples suggests that the mechanism of the response should be taken into account in dental caries and other dental disorders associated with severe fluorosis.
Molecular Analysis of Healing at a Bone-Implant Interface
Authors: Colnot C. , Romero D.M. , Huang S. , Rahman J. , Currey J.A. , Nanci A. , Brunski J.B. , Helms J.A.
Published: January 2009

While bone healing occurs around implants, the extent to which this differs from healing at sites without implants remains unknown. We tested the hypothesis that an implant surface may affect the early stages of healing. In a new mouse model, we made cellular and molecular evaluations of healing at bone-implant interfaces vs. empty cortical defects. We assessed healing around Ti-6Al-4V, poly(L-lactide-co-D,L,-lactide), and 303 stainless steel implants with surface characteristics comparable with those of commercial implants. Our qualitative cellular and molecular evaluations showed that osteoblast differentiation and new bone deposition began sooner around the implants, suggesting that the implant surface and microenvironment around implants favored osteogenesis. The general stages of healing in this mouse model resembled those in larger animal models, and supported the use of this new model as a test bed for studying cellular and molecular responses to biomaterial and biomechanical conditions.
Pre-overloading to Extend Fatigue Life of Cast Clasps
Authors: Mahmoud A.
Published: January 2009

Permanent deformation in bending is associated with the development of residual stresses. The objective of this study was to characterize those residual stresses and test whether they can be manipulated to extend the fatigue lives of cast clasps. Simulations with validated non-linear finite element models were used to characterize the residual stresses in clasps cast from Ti-6Al-7Nb, Co-Cr, and Type IV gold alloys. In addition, two groups of as-cast and pre-overloaded (subjected to a load that produced 20 μm of permanent deformation) Ti-6Al-7Nb clasps (10 specimens each) were subjected to cyclic 0.5-mm deflections at 5 Hz until fatigue. Pre-overloaded specimens demonstrated significantly longer fatigue lives (32,200 ± 17,300 cycles) than did those tested in the as-cast condition (17,900 ± 7600 cycles), consistent with the maximum tensile stress values revealed by finite element analysis.
Apoptosis in Gingival Overgrowth Tissues
Authors: Kantarci A. , Augustin P. , Firatli E. , Sheff M.C. , Hasturk H. , Graves D.T. , Trackman P.C.
Published: January 2009

Variations in the balance between cell proliferation and apoptosis could contribute to the etiology of gingival overgrowth. The aim of this study was to test the hypothesis that, in fibrotic gingival lesions, fibroblast proliferation is stimulated and apoptosis is decreased. Apoptotic index, caspase 3 expression, the proliferative index, FOXO1 expression, and histological inflammation were measured in situ. Analysis of data showed that apoptosis decreased in all forms of gingival overgrowth examined (p < 0.05), and inflammation caused a small but significant increase compared with non-inflamed tissues (p < 0.05). The greatest decrease of apoptosis occurred in the most fibrotic tissues. Cell proliferation was elevated in all forms of gingival overgrowth tested, independent of inflammation (p < 0.05). To identify potential mechanisms of transcriptional regulation of apoptosis, we assessed FOXO1 and caspase 3 expression levels and found them to correlate well with diminished apoptosis. Analysis of data suggests that increased fibroblast proliferation and a simultaneous decrease in apoptosis contribute to gingival overgrowth.
Angiogenesis Inhibitors and the Need for Anti-angiogenic Therapeutics
Authors: Dass C.R. , Tran T.M.N. , Choong P.F.M.
Published: January 2009

Angiogenesis is the formation of new blood vessels from pre-existing vessels to form capillary networks, which, among other diseases, such as diabetic retinopathy and macular degeneration, is particularly important for tumor growth and metastasis. Thus, depriving a tumor of its vascular supply by means of anti-angiogenic agents has been of great interest since its proposal in the 1970s. This review looks at the common angiogenic inhibitors (angiostatin, endostatin, maspin, pigment epithelium-derived factor, bevacizumab and other monoclonal antibodies, and zoledronic acid) and their current status in clinical trials.
A Novel Role for Twist-1 in Pulp Homeostasis
Authors: Galler K.M. , Yasue A. , Cavender A.C. , Bialek P. , Karsenty G. , D’Souza R.N.
Published: January 2009

The molecular mechanisms that maintain the equilibrium of odontoblast progenitor cells in dental pulp are unknown. Here we tested whether homeostasis in dental pulp is modulated by Twist-1, a nuclear protein that partners with Runx2 during osteoblast differentiation. Our analysis of Twist-1(+/−) mice revealed phenotypic changes that involved an earlier onset of dentin matrix formation, increased alkaline phosphatase activity, and pulp stones within the pulp. RT-PCR analyses revealed Twist-1 expression in several adult organs, including pulp. Decreased levels of Twist-1 led to higher levels of type I collagen and Dspp gene expression in perivascular cells associated with the pulp stones. In mice heterozygous for both Twist-1 and Runx2 inactivation, the phenotype of pulp stones appeared completely rescued. These findings suggest that Twist-1 plays a key role in restraining odontoblast differentiation, thus maintaining homeostasis in dental pulp. Furthermore, Twist-1 functions in dental pulp are dependent on its interaction with Runx2.