bluuebunny/crossref_metadata_2025 huggingface dataset:
The Host Cytokine Responses and Protective Immunity in Oropharyngeal Candidiasis
Authors: Dongari-Bagtzoglou A. , Fidel P.L.
Published: January 2009

Over the last three decades, the prevalence of oropharyngeal fungal infections has increased enormously, mainly due to an increasing population of immunocompromised patients, including individuals with HIV infection, transplant recipients, and patients receiving cancer therapy. The vast majority of these infections are caused by Candida species. The presence of cytokines in infected tissues ultimately dictates the host defense processes that are specific to each pathogenic organism. During oral infection with Candida, a large number of pro-inflammatory and immunoregulatory cytokines are generated in the oral mucosa. The main sources of these cytokines are oral epithelial cells, which maintain a central role in the protection against fungal organisms. These cytokines may drive the chemotaxis and effector functions of innate and/or adaptive effector cells, such as infiltrating neutrophils and T-cells in immunocompetent hosts, and CD8+ T-cells in HIV+ hosts. Epithelial cells also have direct anti- Candida activity. Several studies have provided a potential link between lower levels of certain pro-inflammatory cytokines and susceptibility to oral C. albicans infection, suggesting that such cytokines may be involved in immune protection. The exact role of these cytokines in immune protection against oropharyngeal candidiasis is still incompletely understood and requires further investigation. Identification of such cytokines with the ability to enhance anti-fungal activities of immune effector cells may have therapeutic implications in the treatment of this oral infection in the severely immunocompromised host.
Hereditary Blood Coagulation Disorders: Management and Dental Treatment
Authors: Gómez-Moreno G. , Cutando-Soriano A. , Arana C. , Scully C.
Published: January 2009

Patients with hereditary hemostatic disorders, characterized by a tendency to bleeding or thrombosis, constitute a serious challenge in the dental practice. Advances in the medical diagnosis of hemostatic disorders have exposed dental professionals to new patients not amenable to the application of the management protocols associated with other, more well-known, disorders. It is the aim of this paper to review the evidence, to highlight the areas of major concern, and to suggest management regimens for patients with hereditary hemostatic disorders. An extensive review has been made (PubMed, Science Direct, Web of Knowledge, etc.) of literature pertaining to hereditary disorders affecting blood coagulation factors and how they affect the practice of dentistry. Several aspects relating to the care of such patients must be recognized and taken into consideration when dental treatment is planned. Replacement of deficient coagulation factors ensures that safe dental treatment will be carried out. However, the half-life of such coagulation factors requires that dental treatment be specifically planned and adapted to the type of pathology involved.
NF-κB Activation in Human Dental Pulp Stem Cells by TNF and LPS
Authors: Chang J. , Zhang C. , Tani-Ishii N. , Shi S. , Wang C.-Y.
Published: January 2009

Post-natal human dental pulp stem cells (DPSCs) represent a unique precursor population in the dental pulp, which has multipotential and can regenerate a dentin/pulp-like structure. Because the dental pulp is frequently infected by oral bacteria due to dental decay, in this study, we examined whether lipopolysaccharide (LPS) and tumor necrosis factor (TNF) activated the immunologic transcription factor nuclear factor kappa B (NF-κB) in DPSCs. We found that both TNF and LPS activated the I-kappa B kinase complex (IKK) in DPSCs to induce the phosphorylation and degradation of IκBα, resulting in the nuclear translocation of NF-κB. Consistently, both TNF and LPS rapidly induced the expression of the NF-κB-dependent gene interleukin-8 (IL-8). However, unlike in monocytes, we found that LPS could not induce the phosphorylation of the NF-κB active subunit p65 in DPSCs. In summary, our studies suggest that DPSCs may be involved in immune responses during pulpal infection through activating NF-κB.
VIP Inhibits Porphyromonas gingivalis LPS-induced Immune Responses in Human Monocytes
Authors: Foster N. , Cheetham J. , Taylor J.J. , Preshaw P.M.
Published: January 2009

Lipopolysaccharide (LPS) from the Gram-negative pathogen Porphyromonas gingivalis ( Pg) stimulates cytokine secretion in immune cells, and thereby initiates the inflammation associated with periodontitis. Modulation of pro-inflammatory cytokine activity is a plausible therapeutic target in periodontal disease. Vasoactive intestinal peptide (VIP) has a role in immunoregulation, and has been identified as a molecule with therapeutically beneficial immunosuppressive effects in inflammatory and autoimmune conditions. We aimed to investigate the effect of VIP on immune responses induced by Pg LPS in vitro. VIP (10−8 M) significantly (P < 0.05) inhibits TNF-α production by human monocytic THP1 cells stimulated with Pg LPS. In parallel, we showed that VIP inhibits nuclear translocation of NFκB and c-Jun in a time-dependent manner, but does not decrease the expression of CD14 receptors. This is the first report to show the potential of VIP as an immunomodulator of Pg-stimulated inflammatory pathways in human monocytes.
Osteoclastogenic Activity during Mandibular Distraction Osteogenesis
Authors: Wang L.C. , Takahashi I. , Sasano Y. , Sugawara J. , Mitani H.
Published: January 2009

Mandibular distraction osteogenesis is a well-developed clinical modality for the treatment of craniofacial deformities and dental arch discrepancies, in combination with orthodontic treatment. However, in our previous study, orthodontic tooth movement into the distraction gap caused severe root resorption. The present study aimed to clarify the osteoclastogenic activity of cells in the distraction gap. We hypothesized that the gene expression of osteoclastogenic- and osteoclast-supporting molecules in osteoblasts and stromal cells would increase at distraction sites during the consolidation period. An animal model experiment involving rabbits was designed for mandibular distraction osteogenesis and subjected to in situ hybridization analysis. The number of osteoclasts was larger in the distraction gap during the early consolidation period than in normal controls, due to an increase of gene expression for osteoclastogenic cytokines in osteoblasts. It was concluded that osteoclastogenic and osteoclastic activities are stimulated at distraction sites during the early consolidation period.
Cementum and Dentin in Hypophosphatasia
Authors: van den Bos T. , Handoko G. , Niehof A. , Ryan L.M. , Coburn S.P. , Whyte M.P. , Beertsen W.
Published: January 2009

Hypophosphatasia (HPP) often leads to premature loss of deciduous teeth, due to disturbed cementum formation. We addressed the question to what extent cementum and dentin are similarly affected. To this end, we compared teeth from children with HPP with those from matched controls and analyzed them microscopically and chemically. It was observed that both acellular and cellular cementum formation was affected. For dentin, however, no differences in mineral content were recorded. To explain the dissimilar effects on cementum and dentin in HPP, we assessed pyrophosphate (an inhibitor of mineralization) and the expression/activity of enzymes related to pyrophosphate metabolism in both the periodontal ligament and the pulp of normal teeth. Expression of nucleotide pyrophosphatase phosphodiesterase 1 (NPP1) in pulp proved to be significantly lower than in the periodontal ligament. Also, the activity of NPP1 was less in pulp, as was the concentration of pyrophosphate. Our findings suggest that mineralization of dentin is less likely to be under the influence of the inhibitory action of pyrophosphate than mineralization of cementum.
MMP20 Active-site Mutation in Hypomaturation Amelogenesis Imperfecta
Authors: Ozdemir D. , Hart P.S. , Ryu O.H. , Choi S.J. , Ozdemir-Karatas M. , Firatli E. , Piesco N. , Hart T.C.
Published: January 2009

The Amelogenesis Imperfecta (AI) are a group of clinically and genetically heterogeneous disorders that affect enamel formation. To date, mutations in 4 genes have been reported in various types of AI. Mutations in the genes encoding the 2 enamel proteases, matrix metalloproteinase 20 ( MMP20) and kallikrein 4 ( KLK4), have each been reported in a single family segregating autosomal-recessive hypomaturation AI. To determine the frequency of mutations in these genes, we analyzed 15 Turkish probands with autosomal-recessive hypomaturation AI for MMP20 and KLK4 gene mutations. No KLK4 mutations were found. A novel MMP20 mutation (g.16250T>A) was found in one family. This missense mutation changed the conserved active-site His226 residue of the zinc catalytic domain to Gln (p.H226Q). Zymogram analysis demonstrated that this missense mutation abolished MMP20 proteolytic activity. No MMP20 mutations were found in the remaining 14 probands, underscoring the genetic heterogeneity of hypomaturation AI.
CD14 and TLR4 Gene Polymorphisms in Adult Periodontitis
Authors: Laine M.L. , Morré S.A. , Murillo L.S. , van Winkelhoff A.-J. , Peña A.S.
Published: January 2009

Bacterial deposits, smoking, and host genetic factors play a major role in an individual’s predisposition to periodontitis. Bacterial components are recognized by CD14 and toll-like receptor 4 (TLR4), resulting in a NF-κB-based inflammatory response. We hypothesized that functional CD14 and TLR4 polymorphisms contribute to periodontitis susceptibility. We aimed to investigate the occurrence of CD14-260C>T, TLR4 299Asp>Gly, and 399Thr>Ile gene polymorphisms in adult periodontititis. DNA was collected from 100 patients with severe periodontitis and from 99 periodontally healthy controls. The gene polymorphisms were determined by the PCR technique. The presence of the periodontal pathogens Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans, and whether the subjects smoked, was included in the analyses. The CD14-260T/T genotype was found in 34.0% of periodontitis patients and in 20.2% of controls. Logistic regression analysis adjusted for gender, age, smoking, and prevalence of P. gingivalis and A. actinomycetemcomitans showed an association between the CD14-260T/T genotype and periodontitis (P = 0.004, OR 3.0, 95% CI 1.4–6.9). We conclude that the CD14-260T/T genotype contributes to the susceptibility to severe periodontitis in Dutch Caucasians.
Longitudinal Analysis of Heritability for Dental Caries Traits
Authors: Bretz W.A. , Corby P.M. , Schork N.J. , Robinson M.T. , Coelho M. , Costa S. , Melo Filho M.R. , Weyant R.J. , Hart T.C.
Published: January 2009

The role of genetic and environmental factors on dental caries progression in young children was determined. A detailed caries assessment was performed in 2 examinations on 314 pairs of twins initially 1.5 to 8 years old. Surface-based caries prevalence rates (SBCPR) and lesion severity (LSI) were computed. Heritability estimates were calculated by SOLAR software. Analyses were performed on all ages combined and by age group (1.5-< 4; 4–6; > 6). Overall heritability estimates (H) of net increments SBCPRs were H = 30.0 (p < 0.0001), and were greatest for the youngest (H = 30.0) and oldest groups (H = 46.3). Overall LSI heritability estimates [H = 36.1 (p < 0.0001)] were also greatest for the youngest (H = 51.2) and oldest groups (H = 50.6). Similar findings were found for net increments of occlusal surfaces and deep dentinal lesions SBCPRs (H = 46.4–56.2). These findings are consistent with a significant genetic contribution to dental caries progression and severity in both emerging primary and permanent dentitions.
The Growth Hormone Receptor Gene is Associated with Mandibular Height in a Chinese Population
Authors: Zhou J. , Lu Y. , Gao X.H. , Chen Y.C. , Lu J.J. , Bai Y.X. , Shen Y. , Wang B.K.
Published: January 2009

Genetic influences are important in the determination of mandibular morphology, and growth hormone receptor ( GHR) is believed to have an important influence on the growth of craniofacial bone. In this study, we used quantitative trait locus methods to evaluate the relationship between craniofacial morphology and single-nucleotide polymorphisms (SNPs) in GHR in an unselected healthy Chinese population. We systematically screened the 10 exons and nearby introns of GHR and identified 6 SNPs. Using 4 SNPs as markers, we studied the relationships between genotypes and craniofacial linear measurements. Individuals with the genotype CC of polymorphism I526L had a significantly greater mandibular ramus length (condylion-gonion/ articulare-gonion) than those with genotype AC or AA. Haplotype analysis showed that there were also significant differences between the long and short mandibular height groups in an extreme population. Our results indicate that the GHR gene polymorphism I526L is associated with mandibular height in the Chinese population.
Chewing Indicators between Adults with Down Syndrome and Controls
Authors: Hennequin M. , Allison P.J. , Faulks D. , Orliaguet T. , Feine J.
Published: January 2009

Down syndrome induces a neuromotor deficiency that affects the orofacial musculature, and thus could be implicated in the feeding difficulties affecting people with this disease. This study aimed to investigate the differences in chewing indicators between a group of 11 adults with Down syndrome and a group of 12 healthy subjects without Down syndrome. Chewing ability was evaluated by means of video recordings taken during a standardized meal that included 10 natural foods. The variables collected were masticatory time, number of masticatory cycles, chewing frequency, number of open masticatory cycles, and number of food refusals. There were several differences in both directions for masticatory time and number of masticatory cycles between the two groups. In addition, with the exception of purée, the group with Down syndrome had significantly lower mean chewing frequency than the reference group, and was unable to eat all the foods presented.
Biological Approaches to Bone Regeneration by Gene Therapy
Authors: Franceschi R.T.
Published: January 2009

Safe, effective approaches for bone regeneration are needed to reverse bone loss caused by trauma, disease, and tumor resection. Unfortunately, the science of bone regeneration is still in its infancy, with all current or emerging therapies having serious limitations. Unlike current regenerative therapies that use single regenerative factors, the natural processes of bone formation and repair require the coordinated expression of many molecules, including growth factors, bone morphogenetic proteins, and specific transcription factors. As will be developed in this article, future advances in bone regeneration will likely incorporate therapies that mimic critical aspects of these natural biological processes, using the tools of gene therapy and tissue engineering. This review will summarize current knowledge related to normal bone development and fracture repair, and will describe how gene therapy, in combination with tissue engineering, may mimic critical aspects of these natural processes. Current gene therapy approaches for bone regeneration will then be summarized, including recent work where combinatorial gene therapy was used to express groups of molecules that synergistically interacted to stimulate bone regeneration. Last, proposed future directions for this field will be discussed, where regulated gene expression systems will be combined with cells seeded in precise three-dimensional configurations on synthetic scaffolds to control both temporal and spatial distribution of regenerative factors. It is the premise of this article that such approaches will eventually allow us to achieve the ultimate goal of bone tissue engineering: to reconstruct entire bones with associated joints, ligaments, or sutures. Abbreviations used: BMP, bone morphogenetic protein; FGF, fibroblast growth factor; AER, apical ectodermal ridge; ZPA, zone of polarizing activity; PZ, progress zone; SHH, sonic hedgehog; OSX, osterix transcription factor; FGFR, fibroblast growth factor receptor; PMN, polymorphonuclear neutrophil; PDGF, platelet-derived growth factor; IGF, insulin-like growth factor; TGF-β, tumor-derived growth factor β; CAR, coxsackievirus and adenovirus receptor; MLV, murine leukemia virus; HIV, human immunodeficiency virus; AAV, adeno-associated virus; CAT, computer-aided tomography; CMV, cytomegalovirus; GAM, gene-activated matrix; MSC, marrow stromal cell; MDSC, muscle-derived stem cell; VEGF, vascular endothelial growth factor.
Immunomodulation with Enterotoxins for the Generation of Secretory Immunity or Tolerance: Applications for Oral Infections
Authors: Hajishengallis G. , Arce S. , Gockel C.M. , Connell T.D. , Russell M.W.
Published: January 2009

The heat-labile enterotoxins, such as cholera toxin (CT), and the labile toxins types I and II (LT-I and LT-II) of Escherichia coli have been extensively studied for their immunomodulatory properties, which result in the enhancement of immune responses. Despite superficial similarity in structure, in which a toxic A subunit is coupled to a pentameric binding B subunit, different toxins have different immunological properties. Administration of appropriate antigens admixed with or coupled to these toxins by oral, intranasal, or other routes in experimental animals induces mucosal IgA and circulating IgG antibodies that have protective potential against a variety of enteric, respiratory, or genital infections. These include the generation of salivary antibodies that may protect against colonization with mutans streptococci and the development of dental caries. However, exploitation of these adjuvants for human use requires an understanding of their mode of action and the separation of their desirable immunomodulatory properties from their toxicity. Recent findings have revealed that adjuvant action is not critically dependent upon the enzymic activity of the A subunits, and that the isolated B subunits may exert different effects on cells of the immune system than do the intact toxins. Interaction of the toxins with immunocompetent cells is not exclusively dependent upon their conventional ganglioside receptors. Immunomodulatory effects have been observed on dendritic cells, macrophages, CD4+ and CD8+ T-cells, and B-cells. Numerous factors—including the precise form of the toxin adjuvant, properties of the antigen, whether and how they are coupled, route of administration, and species of animal model—affect the outcome, whether this is enhanced humoral and cellular immunity, or specific induced tolerance toward the antigen.
Amelotin—a Novel Secreted, Ameloblast-specific Protein
Authors: Iwasaki K. , Bajenova E. , Somogyi-Ganss E. , Miller M. , Nguyen V. , Nourkeyhani H. , Gao Y. , Wendel M. , Ganss B.
Published: January 2009

We aimed to analyze the differential gene expression in various murine dental tissues, expecting to find novel factors that are involved in tooth formation. We here describe the identification of a novel ameloblast-specific gene, amelotin (AMTN), by differential display polymerase chain-reaction (DD-PCR) analysis of microdissected ameloblasts, odontoblasts, dental pulp, and alveolar bone cells of 10-day-old mouse incisors. The conceptually translated protein sequence was unique and showed significant homology only with its human orthologue. The amelotin genes from mouse and human displayed a similar exon-intron structure and were expressed from loci on chromosomes 5 and 4, respectively, which have been associated with various forms of amelogenesis imperfecta. Expression of amelotin mRNA was restricted to maturation-stage ameloblasts in developing murine molars and incisors. Amelotin protein was efficiently secreted from transfected cells in culture. Taken together, our findings suggest that amelotin is a novel factor produced by ameloblasts that plays a critical role in the formation of dental enamel.
Functional Gene Polymorphisms in Aggressive and Chronic Periodontitis
Authors: Brett P.M. , Zygogianni P. , Griffiths G.S. , Tomaz M. , Parkar M. , D’Aiuto F. , Tonetti M.
Published: January 2009

There is strong evidence that genetic as well as environmental factors affect the development of periodontitis, and some suggestion that aggressive and chronic forms of the disease share the same genetic predisposition. This study addresses the hypothesis that there are both shared and unique genetic associations in these forms of periodontitis. A sample of 51 patients with aggressive disease, 57 patients with chronic disease, and 100 healthy controls was recruited for this study. Ten functional polymorphisms in 7 candidate genes were genotyped. The results show statistically significant (p ≤ 0.05) differences between genotype frequencies in aggressive and controls (IL-1B +3954 & IL-6 −174); chronic and controls (IL-6 −174 & VDR −1056); chronic and aggressive periodontitis (IL-1A −889); and periodontitis as a whole and controls (VDR −1056, TLR-4 399 & IL-6 −174). These results suggest that there are in fact both shared and unique genetic associations in aggressive and chronic periodontitis.
Hydrolytic Stability of Self-etch Adhesives Bonded to Dentin
Authors: Inoue S. , Koshiro K. , Yoshida Y. , De Munck J. , Nagakane K. , Suzuki K. , Sano H. , Van Meerbeek B.
Published: January 2009

Functional monomers chemically interact with hydroxyapatite that remains within submicron hybrid layers produced by mild self-etch adhesives. The functional monomer 10-MDP interacts most intensively with hydroxyapatite, and its calcium salt appeared most hydrolytically stable, as compared with 4-MET and phenyl-P. We investigated the hypothesis that additional chemical interaction of self-etch adhesives improves bond stability. The micro-tensile bond strength (μTBS) of the 10-MDP-based adhesive did not decrease significantly after 100,000 cycles, but did after 50,000 and 30,000 cycles, respectively, for the 4-MET-based and the phenyl-P-based adhesives. Likewise, the interfacial ultrastructure was unchanged after 100,000 thermocycles for the 10-MDP-based adhesive, while that of both the 4-MET- and phenyl-P-based adhesives contained voids and less-defined collagen. The findings of this study support the concept that long-term durability of adhesive-dentin bonds depends on the chemical bonding potential of the functional monomer.
α2 Integrin +807 Polymorphism in Drug-induced Gingival Overgrowth
Authors: Ogino M. , Kido J. , Bando M. , Hayashi N. , Wada C. , Nagata T. , Nishimura F. , Soga Y. , Takashiba S. , Kubota T. , Itagaki M. , Shimada Y. , Tai H. , Yoshie H. , Yamazaki N. , Shinohara Y. , Kataoka M.
Published: January 2009

α2 integrin on fibroblasts is reported to play an important role in the induction of drug-induced gingival overgrowth, which is characterized by excessive accumulation of type I collagen in gingival connective tissue. Silent polymorphism 807 T/C within the α2 integrin gene is associated with high/low α2 integrin expression. The aim of this study was to test the hypothesis that expression of α2 integrin 807 T/C polymorphism correlates with drug-induced gingival overgrowth. A case-control study comparing 136 subjects taking calcium channel blockers (72 with vs. 64 without drug-induced gingival overgrowth) demonstrated that the frequency of the +807 C allele was significantly higher in the case group than in the controls (odds ratio, 3.61; 95% confidence interval, 2.14 – 6.10; P < 0.05). The present findings suggest that the α2 +807 C allele is one of the genetic risk factors for drug-induced gingival overgrowth.
Clock Gene Expression in the Submandibular Glands
Authors: Furukawa M. , Kawamoto T. , Noshiro M. , Honda K.K. , Sakai M. , Fujimoto K. , Honma S. , Honma K. , Hamada T. , Kato Y.
Published: January 2009

Clock genes, which mediate molecular circadian rhythms, are expressed in a circadian fashion in the suprachiasmatic nucleus and in various peripheral tissues. To establish a molecular basis for circadian regulation in the salivary glands, we examined expression profiles of clock-related genes and salivary gland-characteristic genes. Clock-related genes—including Per1, Per2, Cry1, Bmal1, Dec1, Dec2, Dbp, and Reverbα—showed robust circadian expression rhythms in the submandibular glands in 12:12-hour light-dark conditions. In addition, a robust circadian rhythm was observed in amylase 1 mRNA levels, whereas the expression of other salivary-gland-characteristic genes examined was not rhythmic. The Clock mutation resulted in increased or decreased mRNA levels of Per2, Bmal1, Dec1, Dec2, and Dbp, and in Cry1− /− background, Cry2 disruption also increased or decreased mRNA levels of these clock-related genes and the amylase 1 gene. These findings indicate that the Clock- and Cry-dependent molecular clock system is active in the salivary glands.
Polymerization Kinetics of Pre-heated Composite
Authors: Daronch M. , Rueggeberg F.A. , De Goes M.F. , Giudici R.
Published: January 2009

Temperature affects the polymerization behavior of dimethacrylate-based materials. This study describes the influence of pre-polymerization temperature and exposure duration on polymerization kinetics of a commercial dental photo-activated composite at the top and at 2-mm depth. We used the temperature-controlled stage of a diamond-attenuated-total-reflectance unit to pre-set composite temperature between 3° and 60°C. Composite was light-exposed by a conventional quartz-tungsten-halogen curing unit for 5, 10, 20, or 40 sec. Real-time conversion, maximum conversion rate ( R p max), time to achieve R p max, and conversion at R p max were calculated from infrared spectra. Composite pre-warming enhanced maximal polymerization rate and overall monomer conversion (top significantly greater than 2 mm). Time when R p max occurred did not change with temperature, but occurred sooner at the top than at 2-mm depth. Conversion at R p max increased with temperature, allowing more of the reaction to occur prior to vitrification than at room temperature.
Polyelectrolyte Multilayer Film Coating and Stability at the Surfaces of Oral Prosthesis Base Polymers: an in vitro and in vivo Study
Authors: Etienne O. , Picart C. , Taddei C. , Keller P. , Hubsch E. , Schaaf P. , Voegel J.C. , Haikel Y. , Ogier J.A. , Egles C.
Published: January 2009

A new type of coating involving a layer-by-layer technique has been recently reported. This coating is composed of a polyelectrolyte multilayer film that confers specific properties on surfaces to which it is applied. Here, we studied the applicability of such a technique to the coating of oral prostheses, by first testing the construction of polyelectrolyte multilayer films on several polymers used in oral prosthesis bases, and, subsequently, by studying the stability of these coatings in vitro, in human saliva, and in vivo in a rat model. We demonstrated that the multilayered films are able to coat the surfaces of all tested polymers completely, thus increasing their wettability. We also showed that saliva does not degrade the film after 7 days in vitro and after 4 days in vivo. Taken together, our results establish that the layer-by-layer technique is suitable for the coating of oral devices.
Trigeminal Nociceptors Express TLR-4 and CD14: a Mechanism for Pain due to Infection
Authors: Wadachi R. , Hargreaves K.M.
Published: January 2009

Although certain bacterial species appear to be risk factors for pain due to odontogenic infections, comparatively little is known about the potential mechanisms mediating this effect. In this study, we tested the hypothesis that trigeminal nociceptive neurons express the TLR4 or CD14 receptors, thus enabling sensory neurons to detect and respond to tissue levels of bacterial substances such as lipopolysaccharide (LPS). Immunohistochemical analyses of human and rat trigeminal neurons demonstrated that a capsaicin-sensitive subclass of nociceptors (defined by expression of TRPV1, a capsaicin receptor) expresses both TLR4 and CD14. Moreover, human dental pulp collected from patients with caries lesions demonstrated co-localization of TLR4 and CD14, with markers of peripheral sensory neurons. Collectively, these studies indicate that the capsaicin-sensitive subclass of trigeminal nociceptors expresses TLR4 and CD14. These results indicate that pain due to bacterial infections may result, in part, from direct activation of nociceptors by bacterial products such as LPS.
Gingival Tissue and Crevicular Fluid Co-operation in Adult Periodontitis
Authors: Beklen A. , Tüter G. , Sorsa T. , Hanemaaijer R. , Virtanen I. , Tervahartiala T. , Konttinen Y.T.
Published: January 2009

Activated matrix metalloproteinase-3 (MMP-3) can contribute to periodontal ligament destruction in adult periodontitis. Since MMP-3 has been reported to activate proMMP-8 and -9, it was speculated that gingival tissue fibroblast-derived MMP-3 might, in periodontitis, be responsible for activation of gingival crevicular fluid (GCF) neutrophil-derived proMMP-8 and -9. Immunohistochemistry disclosed MMP-3 in gingival fibroblasts in periodontitis. Cultured gingival fibroblasts released only pro-MMP-3 when stimulated with tumor necrosis factor-α. However, Western blot revealed partially activated MMP-3, MMP-8, and MMP-9 in periodontitis GCF. Active MMP-8 (p < 0.05) and MMP-9 (p < 0.05) correlated with the presence of active MMP-3. It seems that resident gingival fibroblasts produce pro-MMP-3 in GCF, where it becomes activated, probably by cathepsin G or elastase released by neutrophils. Active MMP-3 then activates neutrophil-derived pro-MMP-8 and -9. Different tissue compartments/cells exert co-operative actions in mutual local MMP activation cascades.
Pilocarpine-induced Salivation and Thirst in Conscious Rats
Authors: Sato N. , Ono K. , Honda E. , Haga K. , Yokota M. , Inenaga K.
Published: January 2009

The muscarinic receptor agonist pilocarpine is widely used as a sialogogue. It has been well-established that it also induces water intake in animals. However, the mechanisms underlying the relationships between these events are unknown. To address this problem, we examined water intake and parotid salivary secretion in conscious rats. Intraperitoneally injected pilocarpine increased both water intake and salivary secretion. Intracerebroventricularly injected pilocarpine also induced water intake, but not salivary secretion. Intracerebroventricularly applied atropine, a muscarinic receptor antagonist, suppressed the water intake produced by pilocarpine applied intraperitoneally and intracerebroventricularly. However, it did not affect the salivary secretion induced by pilocarpine applied peripherally. We conclude that peripherally applied pilocarpine affects the parotid glands and the thirst center in the central nervous system, while it may induce salivary secretion mainly via peripheral responses, but water intake mainly via the central nervous system.
Overall Activity of All Masticatory Muscles during Lateral Excursion
Authors: Yamaguchi S. , Rikimaru H. , Yamaguchi K. , Itoh M. , Watanabe M.
Published: January 2009

Quantification of the overall activity of every masticatory muscle is requisite for the analysis of stomatognathic function, which has not been accomplished by conventional electromyography. We used positron emission tomography and 18F-fluoro-deoxy-glucose to quantify the overall activity of every masticatory muscle during lateral excursion, and to evaluate the relative contribution of each masticatory muscle to lateral excursion. The present study suggested that lateral and medial pterygoid muscles are more responsible for lateral excursion than are masseter and temporal muscles. In particular, the contralateral lateral pterygoid muscle plays a major role, followed by the contralateral medial pterygoid muscle.
Risk Factors of Early Childhood Caries in a Southeast Asian Population
Authors: van Palenstein Helderman W.H. , Soe W. , van ’t Hof M.A.
Published: January 2009

A retrospective cohort study on ECC and associated factors was conducted among mothers with 25- to 30-month-old infants in a community where prolonged breastfeeding was common practice. All infants who consumed sugary supplementary food or rice that was pre-chewed by the mother, or who fell asleep with the breast nipple in their mouths, had ECC. Infants without those habits, and who were breastfed up to 12 months, had no ECC. Breastfeeding during the day beyond the age of 12 months was not associated with ECC, but infants who were breastfed at night > 2 times had an OR for ECC of 35 (CI 6-186), and those who were exposed to > 15 min per nocturnal feeding had an OR for ECC of 100 (CI 10-995). The present study indicates that, in this population, besides the consumption of sugars and pre-chewed rice, nocturnal breastfeeding after the age of 12 months poses a risk of developing ECC.
Reduced Antigenicity of Type I Collagen and Proteoglycans in Sclerotic Dentin
Authors: Suppa P. , Ruggeri A. , Tay F.R. , Prati C. , Biasotto M. , Falconi M. , Pashley D.H. , Breschi L.
Published: January 2009

Antigenic alterations to the dentin organic matrix may be detected by an immunohistochemical approach. We hypothesized that alterations in the antigenicity of type I collagen and proteoglycans occur in sclerotic dentin under caries lesions. Transverse sections were prepared from carious teeth in the sclerotic zone and normal hard dentin. A double-immunolabeling technique was performed on these sections, with anti-type I collagen and anti-chondroitin 4/6 sulfate monoclonal primary antibodies. We used gold-conjugated secondary antibodies to visualize the distribution of intact collagen fibrils and proteoglycans by high-resolution SEM. For sclerotic dentin, labeling densities were 19.57 ± 3.01/μm2 for collagen and 9.84 ± 2.62/μm2 for proteoglycans. For normal hard dentin, values were 35.20 ± 2.73/μm2 and 17.03 ± 1.98/μm2, respectively. Distribution of intact collagen fibrils and proteoglycans in sclerotic dentin was significantly lower than in normal hard dentin. Reductions in antigenicity from the organic matrix of sclerotic dentin under caries lesions raise concern about the potential of intrafibrillar remineralization.
Amelogenin-mediated Regulation of Osteoclastogenesis, and Periodontal Cell Proliferation and Migration
Authors: Hatakeyama J. , Philp D. , Hatakeyama Y. , Haruyama N. , Shum L. , Aragon M.A. , Yuan Z. , Gibson C.W. , Sreenath T. , Kleinman H.K. , Kulkarni A.B.
Published: January 2009

We previously reported that amelogenin isoforms M180 and leucine-rich amelogenin peptide (LRAP) are expressed in the periodontal region, and that their absence is associated with increased cementum defects in amelogenin-knockout (KO) mice. The aim of the present study was to characterize the functions of these isoforms in osteoclastogenesis and in the proliferation and migration of cementoblast/periodontal ligament cells. The co-cultures of wild-type (WT) osteoclast progenitor and KO cementoblast/periodontal ligament cells displayed more tartrate-resistant acid phosphatase (TRAP)-positive cells than the co-cultures of WT cells. The addition of LRAP to both co-cultures significantly reduced RANKL expression and the TRAP-positive cells. Proliferation and migration rates of the KO cementoblast/periodontal ligament cells were lower than those of WT cells and increased with the addition of either LRAP or P172 (a porcine homolog of mouse M180). Thus, we demonstrate the regulation of osteoclastogenesis by LRAP, and the proliferation and migration of cementoblast/periodontal ligament cells by LRAP and P172.
Differential uPA Expression by TGF-β1 in Gingival Fibroblasts
Authors: Smith P.C. , Martínez J.
Published: January 2009

Transforming Growth Factor-β1 (TGF-β1) plays a key role in connective tissue remodeling and inflammation. Under pathological conditions, like periodontal disease, fibroblasts may display an altered response to this growth factor. To investigate this question, we have studied whether TGF-β1 may differentially regulate the expression of urokinase at the protein level in primary cultures of fibroblasts derived from healthy gingiva, granulation tissue from gingival wounds, and chronic periodontal disease. We observed that TGF-β1 may repress urokinase expression in healthy gingival fibroblasts and promote its production in granulation-tissue fibroblasts. A significant correlation was found between expression of the myofibroblast marker α-smooth-muscle actin and stimulation of urokinase production by TGF-β1. Immunostaining of gingival wounds showed that myofibroblasts were involved in urokinase production. TGF-β1-stimulated urokinase expression was blocked after inhibition of the c-jun-NH2 terminal kinase signaling pathway. We propose that stimulation of urokinase production by TGF-β1 is involved in the responses of activated fibroblasts to tissue injury.
Rosiglitazone Reduces the Evolution of Experimental Periodontitis in the Rat
Authors: Di Paola R. , Mazzon E. , Maiere D. , Zito D. , Britti D. , De Majo M. , Genovese T. , Cuzzocrea S.
Published: January 2009

The peroxisome proliferator-activated receptor-γ (PPAR-γ) receptor appears to play a pivotal role in the regulation of cellular proliferation and inflammation. Recent evidence also suggests that rosiglitazone, a PPAR-γ agonist, reduces acute and chronic inflammation. We hypothesized that rosiglitazone would attenuate periodontal inflammation. In the present study, we investigated the effects of rosiglitazone in a rat model of ligature-induced periodontitis. At day 8, ligation significantly induced an increase in neutrophil infiltration, as well as of gingivomucosal tissue expression of iNOS, nitrotyrosine formation, and poly (ADP-ribose) polymerase activation. Ligation significantly increased Evans blue extravasation in gingivomucosal tissue and alveolar bone destruction. Intraperitoneal injection of rosiglitazone (10 mg/kg 10% DMSO daily for 8 days) significantly decreased all of the parameters of inflammation, as described above. Analysis of these data demonstrated that rosiglitazone exerted an anti-inflammatory role during experimental periodontitis, and was able to ameliorate the tissue damage associated with ligature-induced periodontitis.
Articaine is More Effective than Lidocaine or Mepivacaine in Rat Sensory Nerve Conduction Block in vitro
Authors: Potočnik I. , Tomšič M. , Sketelj J. , Bajrović F.F.
Published: January 2009

The reasons for the relatively high failure rate after inferior alveolar nerve block in dentistry are not fully understood. Therefore, the effectiveness of different anesthetic solutions (2% and 4% lidocaine, 3% mepivacine, 2% and 4% articaine) in depressing the compound action potential amplitude of the sensory fibers in the rat sural nerve was examined under strictly controlled conditions in vitro. After application of an anesthetic solution and stimulation of the nerve with a supramaximal electrical stimulus, a complete disappearance of the compound action potential of the C fibers, but not of the A fibers, was observed in all the experimental groups. Both 2% and 4% articaine more effectively depressed the compound action potential of the A fibers than did other anesthetic solutions. These results are discussed in the light of recent clinical reports finding no differences in the effectiveness between 4% articaine and 2% lidocaine regarding the inferior alveolar nerve block.
Fluoride Varnish Efficacy in Preventing Early Childhood Caries
Authors: Weintraub J.A. , Ramos-Gomez F. , Jue B. , Shain S. , Hoover C.I. , Featherstone J.D.B. , Gansky S.A.
Published: January 2009

To determine the efficacy of fluoride varnish (5% NaF, Duraphat®, Colgate) added to caregiver counseling to prevent early childhood caries, we conducted a two-year randomized, dental-examiner-masked clinical trial. Initially, 376 caries-free children, from low-income Chinese or Hispanic San Francisco families, were enrolled (mean age ± standard deviation, 1.8 ± 0.6 yrs). All families received counseling, and children were randomized to the following groups: no fluoride varnish, fluoride varnish once/year, or fluoride varnish twice/year. An unexpected protocol deviation resulted in some children receiving less active fluoride varnish than assigned. Intent-to-treat analyses showed a fluoride varnish protective effect in caries incidence, p < 0.01. Analyzing the number of actual, active fluoride varnish applications received resulted in a dose-response effect, p < 0.01. Caries incidence was higher for ‘counseling only’ vs. ‘counseling + fluoride varnish assigned once/year’ (OR = 2.20, 95% CI 1.19–4.08) and ‘twice/year’ (OR = 3.77, 95% CI 1.88–7.58). No related adverse events were reported. Fluoride varnish added to caregiver counseling is efficacious in reducing early childhood caries incidence.
Coordination of Tongue Pressure and Jaw Movement in Mastication
Authors: Hori K. , Ono T. , Nokubi T.
Published: January 2009

The tongue plays an important role in mastication and swallowing by its contact with the hard palate. Using an experimental palatal plate with 7 pressure sensors, and recording jaw movement using mandibular kinesiography, we assessed, in healthy subjects, the coordination of tongue and jaw movements during the entire masticatory sequence of solids, by measuring tongue pressure against the hard palate. Tongue pressure appeared during the occlusal phase, reached a peak near the start of opening, and disappeared during opening. Specific patterns in order, duration, and magnitude of tongue pressure were seen at the 7 pressure sensors in each chewing stroke. Magnitude and duration were significantly larger in the late stage of chewing (8 strokes before initial swallowing) than in the early stage (until 8 strokes after starting mastication). The normal pattern of tongue contact against the hard palate, control of tongue activity, and coordination with jaw movement during mastication is described.
Protective and Destructive Immunity in the Periodontium: Part 1—Innate and Humoral Immunity and the Periodontium
Authors: Teng Y.-T.A.
Published: January 2009

Based on the results of recent research in the field, the present paper will discuss the protective and destructive aspects of the innate vs. adaptive (humoral and cell-mediated) immunity associated with the bacterial virulent factors or antigenic determinants during periodontal pathogenesis. Attention will be focused on: (i) the Toll-like receptors (TLR), the innate immune repertoire for recognizing the unique molecular patterns of microbial components that trigger innate and adaptive immunity for effective host defenses, in some general non-oral vs. periodontal microbial infections; (ii) T-cell-mediated immunity, Th-cytokines, and osteoclastogenesis in periodontal disease progression; and (iii) some molecular techniques developed and used to identify critical microbial virulence factors or antigens associated with host immunity (using Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis as the model species). Therefore, further understanding of the molecular interactions and mechanisms associated with the host’s innate and adaptive immune responses will facilitate the development of new and innovative therapeutics for future periodontal treatments. Abbreviations used in the paper are as follows: A. actinomycetemcomitans ( Aa), Actinobacillus actinomycetemcomitans; Ab, antibody; DC, dendritic cells; mAb, monoclonal antibody; pAb, polyclonal antibody; PAMP, pathogen-associated molecular patterns; P. gingivalis ( Pg), Porphyromonas gingivalis; and TLR, Toll-like receptors.
Silibinin Inhibits Invasion of Oral Cancer Cells by Suppressing the MAPK Pathway
Authors: Chen P.-N. , Hsieh Y.-S. , Chiang C.-L. , Chiou H.-L. , Yang S.-F. , Chu S.-C.
Published: January 2009

Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity. Here, we provide molecular evidence associated with the anti-metastatic effect of silibinin by showing a marked inhibition of the invasion and motility of SCC-4 tongue cancer cells, with 89% and 66.4% of inhibition, respectively, by 100 μM of silibinin. This effect was associated with a reduced expression of MMP-2 and u-PA, together with an enhanced expression of TIMP-2 and PAI-1. Silibinin also exerted an inhibitory effect on the phosphorylation of ERK1/2. Additionally, pre-treatment of SCC-4 cancer cells with 10 and 20 μM of U0126, a specific MEK inhibitor, resulted in a reduced expression of MMP-2 (18.7 and 51.4%) and u-PA (19.2 and 48.9%) concomitantly with a marked inhibition of cell invasion (13.7 and 45.7%). Finally, silibinin was evidenced by its inhibition of the metastasis of Lewis lung carcinoma (LLC) cells in vivo. These results suggested that silibinin can reduce the invasion and metastasis of tumor cells, and such a characteristic may be of great value in the development of a potential cancer therapy.
Compressive Force Induces Osteoblast Apoptosis via Caspase-8
Authors: Goga Y. , Chiba M. , Shimizu Y. , Mitani H.
Published: January 2009

Periodontal remodeling during orthodontic tooth movement is a result of mechanical stresses. The application of excessive orthodontic force induces cell death. However, the nature of compressive force-induced cell death is unclear. We examined whether the in vitro application of continuous compressive force would induce apoptosis in human osteoblast-like cells (MG-63 cells), and investigated the mechanism by which apoptosis was initiated. The cells became aligned irregularly, and cell viability decreased, indicating that the compressive force caused cell death. According to the TUNEL analysis, the number of apoptotic cells increased significantly in a time-and force-dependent manner. Caspase-3 activity increased with the magnitude of the compressive force, and this effect was reduced significantly by a caspase-8 inhibitor, whereas a caspase-9 inhibitor had no such effect. We conclude that the in vitro application of compressive force can induce apoptosis in MG-63 cells through the activation of caspase-3 via the caspase-8 signaling cascade.
Hypermethylation of CpGs in the Promoter of the COL1A1 Gene in the Aged Periodontal Ligament
Authors: Ohi T. , Uehara Y. , Takatsu M. , Watanabe M. , Ono T.
Published: January 2009

Although the human periodontal ligament shows age-associated histological alterations, the molecular mechanisms are not yet understood. We previously found that COL1A1 gene expression declines with age. In this study, we asked whether DNA methylation in the regulatory region of the gene alters in the aging process, as a possible cause of the decline. The method used was a bisulfite modification of cytosine and nucleotide sequencing of DNA. While the 1st intron region was kept demethylated at young and old ages, the levels of methylation at most CpG sites in the proximal and distal regions of the promoter showed elevation at older ages. Analysis of the data indicates the possible importance of DNA hypermethylation in the promoter region for the age-associated decrease of COL1A1 gene expression.
Functional α1-Adrenoceptor Subtypes in Human Submandibular Glands
Authors: Huang Z. , Wu L.L. , Zhang Y.Y. , Gao Y. , Yu G.Y.
Published: January 2009

α1-Adrenoceptor has been discovered to exist in many human tissues and mediates important physiological functions. The purpose of this study was to detect the expression, distribution, and function of α1-adrenoceptor subtypes in human submandibular glands. α1A- and α1B-Adrenoceptor mRNAs were identified by reverse-transcription/polymerase chain-reaction (RT-PCR), and their proteins were detected by Western blotting. No expression of the α1D-adrenoceptor mRNA and protein was found. By in situ hybridization and immunohistochemistry, α1A- and α1B-adrenoceptor mRNAs and proteins were shown to be widespread in both ductal and acinar cells. By confocal microscopy, phenylephrine (stimulating both α1A- and α1B-adrenoceptors) or A61603 (α1A-selective agonist) induced an increase in intracellular calcium by 2.33 ± 0.18-fold and 1.81 ± 0.43-fold, respectively, while 5-methylurapidil (α1A-selective antagonist) partly blocked calcium mobility stimulated by phenylephrine. The results indicated that functional α1A- and α1B-adrenoceptors were expressed in human submandibular glands, and might contribute to the regulation of saliva synthesis and secretion.