bluuebunny/crossref_metadata_2025 huggingface dataset:
Staphylococcus aureus and Other Bacteria in Untreated Periodontitis
Authors: Fritschi B. Zinsli , Albert-Kiszely A. , Persson G.R.
Published: January 2009

Whether the subgingival microbiota differ between individuals with chronic and those with aggressive periodontitis, and whether smoking influences bacterial composition, is controversial. We hypothesized that the subgingival microbiota do not differ between sites in individuals with chronic or aggressive periodontitis, or by smoking status. Bacterial counts and proportional distributions were assessed in 84 individuals with chronic periodontitis and 22 with aggressive periodontitis. No differences in probing pocket depth by periodontal status were found (mean, 0.11 mm; 95% CI, 0.6 to 0.8, p = 0.74). Including Staphylococcus aureus, Parvimonas micra, and Prevotella intermedia, 7/40 species were found at higher levels in those with aggressive periodontitis (p < 0.001). Smokers had higher counts of Tannerella forsythia (p < 0.01). The prevalence of S. aureus in non-smokers with aggressive periodontitis was 60.5%. The null hypothesis was rejected, in that P. intermedia, S. aureus, and S. mutans were robust in diagnosing sites in individuals with aggressive periodontitis. S. aureus, S. sanguinis, and T. forsythia differentiated smoking status.
Surface Analysis of Etched Molar Enamel by Gas Adsorption
Authors: Orellana M.F. , Nelson A.E. , Carey J.P.R. , Heo G. , Boychuk D.G , Major P.W.
Published: January 2009

Much research has been devoted to the study of etched enamel, since it is critical to bonding. Currently, there are no precise data regarding the etched-enamel specific surface area. The aim of this study was to characterize, by two different methods, the surface of human dental enamel in vitro after being etched. It was hypothesized that differences would be observed between specimens in terms of specific surface area and grade of etching. Sixteen third molar enamel samples were etched for 30 sec with 37% phosphoric acid prior to being viewed by SEM. Etched enamel surfaces were graded according to the Galil and Wright classification. The total surface area of etched samples was determined by the BET gas absorption method. A substantial variability in total surface area was observed between and among samples. A Pearson’s Correlation Coefficient showed a lack of relationship between etch pattern and total surface area.
Clinically Relevant Cell Sources for TMJ Disc Engineering
Authors: Johns D.E. , Wong M.E. , Athanasiou K.A.
Published: January 2009

Tissue-engineering of the temporomandibular joint (TMJ) disc aims to provide patients with TMJ disorders an option to replace diseased tissue with autologous, functional tissue. This study examined clinically relevant cell sources by comparing costal chondrocytes, dermal fibroblasts, a mixture of the two, and TMJ disc cells in a scaffoldless tissue-engineering approach. It was hypothesized that all constructs would produce matrix relevant to the TMJ disc, but the mixture constructs were expected to appear most like the TMJ disc constructs. Costal chondrocyte and mixture constructs were morphologically and biochemically superior to the TMJ disc and dermal fibroblast constructs, and their compressive properties were not significantly different. Costal chondrocyte constructs produced almost 40 times more collagen and 800 times more glycosaminoglycans than did TMJ constructs. This study demonstrates the ability of costal chondrocytes to produce extracellular matrix that may function in a TMJ disc replacement.
Implications for Creutzfeldt-Jakob Disease (CJD) in Dentistry: a Review of Current Knowledge
Authors: Walker J.T. , Dickinson J. , Sutton J.M. , Marsh P.D. , Raven N.D.H.
Published: January 2009

This review explores our current understanding of the risks of (variant) Creutzfeldt-Jakob disease transmission via dental practice, and whether they merit the rigorous enforcement of improved standards of instrument cleaning and decontamination. The recognition of prions as novel infectious agents in humans has caused significant concern among the public and medical professionals alike. Creutzfeldt-Jakob disease (CJD) in humans has been shown to be transmissible via several routes, including transplantation, contaminated medical products, and via neurosurgery. While the likelihood of transmission via dentistry is undoubtedly very low, this may be amplified considerably by unknown risk factors, such as disease prevalence (particularly in the UK), altered tissue distribution of vCJD, and the failure of decontamination processes to address the inactivation of prions adequately. Since current diagnostic techniques are unable to detect PrPSc in human dental tissues, there is limited evidence for the presence of infectivity. Given these uncertainties, the control of risk by reinforced and improved decontamination practices seems the most appropriate response.
IL-1β and TNF-α Regulate IL-6-type Cytokines in Gingival Fibroblasts
Authors: Palmqvist P. , Lundberg P. , Lundgren I. , Hänström L. , Lerner U.H.
Published: January 2009

Interleukin-6 (IL-6)-type cytokines are pleiotropic molecules capable of stimulating bone resorption and expressed by numerous cell types. In the present study, we tested the hypothesis that gingival fibroblasts may exert local osteotropic effects through production of IL-6 and related cytokines. IL-6-type cytokine expression and regulation by IL-1β and tumor necrosis factor-α (TNF-α) were studied in fibroblasts from the non-inflamed gingiva of healthy individuals. Constitutive mRNA expression of IL-6, IL-11, and leukemia inhibitory factor (LIF), but not of oncostatin M (OSM), was demonstrated, as was concentration-dependent stimulation of IL-6 and LIF mRNA and of protein by IL-1β and TNF-α. IL-11 mRNA and protein were concentration-dependently stimulated by IL-1β. The signaling pathway involved in IL-6 and LIF mRNA stimulation involved MAP kinases, but not NF-κB. The findings support the view that resident cells may influence the pathogenesis of periodontal disease through osteotropic IL-6-type cytokine production mediated by activation of MAP kinases. Abbreviations: IL-1α (interleukin-1α); IL-1β (interleukin-1β); IL-6 (interleukin-6); IL-11 (interleukin-11); LIF (leukemia inhibitory factor); OSM (oncostatin M); α(1)-coll. I (α(1)-collagen I); ALP (alkaline phosphatase); BMP-2 (bone morphogenetic protein-2); OC (osteocalcin); BSP (bone sialoprotein); TNFR I (tumor necrosis factor receptor I); TNFR II (tumor necrosis factor receptor II); IL-1R1 (interleukin-1 receptor 1); GAPDH (glyceraldehyde-3-phosphate dehydrogenase); RPL13A (ribosomal protein L13A); mRNA (messenger ribonucleic acid); cDNA (complementary deoxyribonucleic acid); PCR (polymerase chain-reaction); BCA (bicinchoninic acid); ELISA (enzyme-linked immunosorbent assay); α-MEM (α modification of Minimum Essential Medium); and FCS (fetal calf serum).
PTCH1 and SMO Gene Alterations in Keratocystic Odontogenic Tumors
Authors: Sun L.-S. , Li X.-F. , Li T.-J.
Published: January 2009

Keratocystic odontogenic tumors (KCOTs, previously known as odontogenic keratocysts) are aggressive jaw lesions that may occur in isolation or in association with nevoid basal cell carcinoma syndrome (NBCCS). Mutations in the PTCH1 ( PTCH) gene are responsible for NBCCS and are related in tumors associated with this syndrome. Mutations in the SMO gene have been identified in basal cell carcinoma and in medulloblastoma, both of which are features of NBCCS. To clarify the role of PTCH1 and SMO in KCOTs, we undertook mutational analysis of PTCH1 and SMO in 20 sporadic and 10 NBCCS-associated KCOTs, and for SMO, 20 additional cases of KCOTs with known PTCH1 status were also included. Eleven novel (1 of which occurred twice) and 5 known PTCH1 mutations were identified. However, no pathogenic mutation was detected in SMO. Our findings suggest that mutations are rare in SMO, but frequent in PTCH1 in sporadic and NBCCS-associated KCOTs. Abbreviations: NBCCS, nevoid basal cell carcinoma syndrome; KCOTs, keratocystic odontogenic tumors; BCCs, basal cell carcinomas.
Changes in Resin-infiltrated Dentin Stiffness after Water Storage
Authors: Chiaraputt S. , Mai S. , Huffman B.P. , Kapur R. , Agee K.A. , Yiu C.K.Y. , Chan D.C.N. , Harnirattisai C. , Arola D.D. , Rueggeberg F.A. , Pashley D.H. , Tay F.R.
Published: January 2009

Plasticization of polymers by water sorption lowers their mechanical properties in a manner that is predictable by the polarity of their component resins. This study tested the hypothesis that when adhesive resins were used to create resin-infiltrated dentin, the reductions in their flexural moduli after water storage would be lowered proportional to their hydrophilic characteristics. Three increasingly hydrophilic resin blends were used to fabricate polymer beams and macro-hybrid layer models of resin-infiltrated dentin for testing with a miniature three-point flexure device, before and after 1–4 weeks of water storage. Flexural modulus reductions in macro-hybrid layers were related to, and more extensive than, reductions in the corresponding polymer beams. Macro-hybrid layers that were more hydrophilic exhibited higher percent reductions in flexural modulus, with the rate of reduction proportional to the Hoy’s solubility parameters for total intermolecular attraction forces (δt) and polar forces (δp) of the macro-hybrid layers.
Cooperation of Phosphate Monomer and Silica Modification on Zirconia
Authors: Tanaka R. , Fujishima A. , Shibata Y. , Manabe A. , Miyazaki T.
Published: January 2009

Ceramic restorations with resin-based adhesive systems have been the focus of recent attention in clinical dentistry. Yttrium-oxide-partially-stabilized zirconia (YPSZ) ceramics have optimized physical properties and exhibit favorable fracture toughness, though their bonding properties are problematic. Although functional phosphate monomers and silica-coating by tribochemical modification were expected to improve the bonding properties between YPSZ ceramics and resin-based adhesives, these two methods remain controversial. This study evaluated the efficiency of silica-coating by tribochemical modification of YPSZ ceramics. The application of phosphate monomer and a silane coupling agent on silica-coated YPSZ was also investigated. The silica-coating of YPSZ ceramics by tribochemical modification was not efficient, given the higher mechanical toughness of the densely sintered ceramics. Stable shear bond strength was achieved on silica-coated YPSZ ceramics with the cooperative interaction of phosphate monomer and silane coupling.
Self-assembling Peptides: From Bio-inspired Materials to Bone Regeneration
Authors: Semino C. E.
Published: January 2009

In recent years, the development of new biomaterials with specifications for tissue and organ functional requirements—such as proper biological, structural, and biomechanical properties as well as designed control for biodegradation and therapeutic drug-release capacity—is the main aim of many academic and industrial programs. Hence, the concept of molecular self-assembly is the driving force for the development of new biomaterials that support the growth and functional differentiation of cells and tissues in a controlled manner. The discovery, properties, and development of self-assembling peptides to be used as three-dimensional (3D) scaffolds based on their similarity (in structure and mechanical features) to extracellular matrices are described. Self-assembling peptides can be used for in vitro applications for cell 3D culture as well as in vivo for tissue regeneration such as bone and optical nerve repair, as well as for drug delivery of mediators to improve therapy, as in the case of myocardial infarction. Finally, the use of self-assembling materials in combination with a bioengineering platform is proposed to assist functional bone regeneration in cases of larger bone defects, including exposed fractures due to trauma and spinal disorders dealing with high loadings, as well as replacement of big bone structures due to tumors.
Proliferation and Differentiation of MC3T3-E1 Cells on Calcium Phosphate/Chitosan Coatings
Authors: Wang J. , de Boer J. , de Groot K.
Published: January 2009

The incorporation of chitosan into electro-deposited calcium phosphate (CaP) coatings increases bone marrow stromal cell attachment. We hypothesized that such electrodeposited CaP/chitosan coatings can also enhance the proliferative ability and differentiation potential of osteoblasts. To verify this hypothesis, we cultured osteoblast-like MC3T3-E1 cells on these CaP coatings. It was found that MC3T3-E1 cells cultured on the electrodeposited CaP/chitosan coatings had cell proliferation rates higher than those on the electrodeposited CaP coatings. At the same time, both alkaline phosphatase activity and collagen expression were increased, and both bone sialoprotein and osteocalcin genes were up-regulated when MC3T3-E1 cells were cultured on the electrodeposited CaP/chitosan coatings. Additionally, within the range of selected chitosan concentrations in solution, no significant difference was found between the CaP/chitosan coatings. Our results suggest that the electrodeposited CaP/chitosan coatings are favorable to the proliferation and differentiation of MC3T3-E1 cells, which may endow them with great potential for future applications.
MMP-3 Response to Compressive Forces in vitro and in vivo
Authors: Chang H.-H. , Wu C.-B. , Chen Y.-J. , Weng C.-Y. , Wong W.-P. , Chen Y.-J. , Chang B.-E. , Chen M.-H. , Yao C.-C.J.
Published: January 2009

During orthodontic tooth movement, bone resorption occurs at the compression site. However, the mechanism underlying resorption remains unclear. Applying compressive force to human osteoblast-like cells grown in a 3D collagen gel, we examined gene induction by using microarray and RT-PCR analysis. Among 43 genes exhibiting significant changes, cyclo-oxygenase-2, ornithine decarboxylase, and matrix metalloproteinase-3 (MMP-3) were up-regulated, whereas membrane-bound interleukin-1 receptor accessory protein was down-regulated. The MMP-3 protein increases were further confirmed by Western blot. To ascertain whether MMP-3 is up-regulated in vivo by orthodontic force, we examined human bone samples at the compressive site by realigning the angulated molars. Immunohistochemical staining revealed MMP-3 distributed along the compressive site of the bony region within 3 days of compression. Since MMP-3 participates in degradation of a wide range of extracellular matrix molecules, we propose that MMP-3 plays an important role in bone resorption during orthodontic tooth movement.
Tooth Agenesis: from Molecular Genetics to Molecular Dentistry
Authors: Matalova E. , Fleischmannova J. , Sharpe P.T. , Tucker A.S.
Published: January 2009

Tooth agenesis may originate from either genetic or environmental factors. Genetically determined hypodontic disorders appear as isolated features or as part of a syndrome. Msx1, Pax9, and Axin2 are involved in non-syndromic hypodontia, while genes such as Shh, Pitx2, Irf6, and p63 are considered to participate in syndromic genetic disorders, which include tooth agenesis. In dentistry, artificial tooth implants represent a common solution to tooth loss problems; however, molecular dentistry offers promising solutions for the future. In this paper, the genetic and molecular bases of non-syndromic and syndromic hypodontia are reviewed, and the advantages and disadvantages of tissue engineering in the clinical treatment of tooth agenesis are discussed.
Randomized Study of Phentolamine Mesylate for Reversal of Local Anesthesia
Authors: Laviola M. , McGavin S.K. , Freer G.A. , Plancich G. , Woodbury S.C. , Marinkovich S. , Morrison R. , Reader A. , Rutherford R.B. , Yagiela J.A.
Published: January 2009

Local anesthetic solutions frequently contain vasoconstrictors to increase the depth and/or duration of anesthesia. Generally, the duration of soft-tissue anesthesia exceeds that of pulpal anesthesia. Negative consequences of soft-tissue anesthesia include accidental lip and tongue biting as well as difficulty in eating, drinking, speaking, and smiling. A double-blind, randomized, multicenter, Phase 2 study tested the hypothesis that local injection of the vasodilator phentolamine mesylate would shorten the duration of soft-tissue anesthesia following routine dental procedures. Participants (122) received one or two cartridges of local anesthetic/vasoconstrictor prior to dental treatment. Immediately after treatment, 1.8 mL of study drug (containing 0.4 mg phentolamine mesylate or placebo) was injected per cartridge of local anesthetic used. The phentolamine was well-tolerated and reduced the median duration of soft-tissue anesthesia in the lip from 155 to 70 min (p < 0.0001).
Emdogain Stimulates Matrix Degradation by Osteoblasts
Authors: Goda S. , Inoue H. , Kaneshita Y. , Nagano Y. , Ikeo Y. T. , Iida J. , Domae N.
Published: January 2009

Emdogain has been used clinically for periodontal regeneration, although the underlying molecular mechanisms are not clear at present. In this study, we hypothesized that Emdogain stimulated degradation of type I collagen via osteoblasts. We showed that Emdogain enhanced cell-mediated degradation of type I collagen in an MMP-dependent manner. Although MG-63 cells spontaneously produced a zymogen form of MMP-1, treatment with Emdogain significantly induced the generation of the active form of this enzyme. We demonstrated that MMP-3 was produced from MG63 cells in response to Emdogain in a MEK1/2-dependent manner. Concomitantly, blocking of MEK1/2 activation by U0126 significantly inhibited the generation of the active form of MMP-1 without affecting the total production of this collagenase. These results suggest that Emdogain facilitates tissue regeneration through the activation of the collagenase, MMP-1, that degrades matrix proteins in bone tissue microenvironments.
Mussel-designed Protective Coatings for Compliant Substrates
Authors: Holten-Andersen N. , Waite J. H.
Published: January 2009

The byssus of marine mussels has attracted attention as a paradigm of strong and versatile underwater adhesion. As the first of the 3,4-dihydroxyphenylalanine (Dopa)-containing byssal precursors to be purified, Mytilus edulis foot protein-1 (mefp-1) has been much investigated with respect to its molecular structure, physical properties, and adsorption to surfaces. Although mefp-1 undoubtedly contributes to the durability of byssus, it is not directly involved in adhesion. Rather, it provides a robust coating that is 4–5 times stiffer and harder than the byssal collagens that it covers. Protective coatings for compliant tissues and materials are highly appealing to technology, notwithstanding the conventional wisdom that coating extensibility can be increased only at the expense of hardness and stiffness. The byssal cuticle is the only known coating in which high compliance and hardness co-exist without mutual detriment; thus, the role of mefp-1 in accommodating both parameters deserves further study.
Ti Nano-nodular Structuring for Bone Integration and Regeneration
Authors: Ogawa T. , Saruwatari L. , Takeuchi K. , Aita H. , Ohno N.
Published: January 2009

Nanostructuring technology has been proven to create unique biological properties in various biomaterials. Here we present a discovered phenomenon of titanium nano-nodular self-assembly that occurs during physical vapor depositions of titanium (Ti) onto specifically conditioned micro-textured titanium surfaces, and test a hypothesis that the Ti nanostructure has the potential to enhance bone-titanium integration. The nanostructure creation effectively provided geometrical undercut and increased the surface area by up to 40% compared with the acid-etched surface with microtopography. Depending on the size control, the nano-nodules can be added without smearing the existing micro-texture, creating a nano-micro-hybrid architecture. Titanium implants with 560-nm nano-nodules produced 3.1 times greater strength of osseointegration than those with an acid-etched surface in a rat femur model. The discovered titanium nano-nodular self-structuring has been proven feasible on biocompatible materials other than titanium, offering new avenues for the development of implant surfaces and other implantable materials for better bone-generative and -regenerative potential.
Bioengineered Dental Tissues Grown in the Rat Jaw
Authors: Duailibi S.E. , Duailibi M.T. , Zhang W. , Asrican R. , Vacanti J.P. , Yelick P.C.
Published: January 2009

Our long-term objective is to develop methods to form, in the jaw, bioengineered replacement teeth that exhibit physical properties and functions similar to those of natural teeth. Our results show that cultured rat tooth bud cells, seeded onto biodegradable scaffolds, implanted into the jaws of adult rat hosts and grown for 12 weeks, formed small, organized, bioengineered tooth crowns, containing dentin, enamel, pulp, and periodontal ligament tissues, similar to identical cell-seeded scaffolds implanted and grown in the omentum. Radiographic, histological, and immunohistochemical analyses showed that bioengineered teeth consisted of organized dentin, enamel, and pulp tissues. This study advances practical applications for dental tissue engineering by demonstrating that bioengineered tooth tissues can be regenerated at the site of previously lost teeth, and supports the use of tissue engineering strategies in humans, to regenerate previously lost and/or missing teeth. The results presented in this report support the feasibility of bioengineered replacement tooth formation in the jaw.
EGFR in Enamel Matrix Derivative-induced Gingival Fibroblast Mitogenesis
Authors: Zeldich E. , Koren R. , Dard M. , Nemcovsky C. , Weinreb M.
Published: January 2009

We previously reported that EMD (Enamel Matrix Derivative) induces proliferation of human gingival fibroblasts via activation of Extracellular Regulated Kinase (ERK), and this study assessed the possible mediatory role of EGFR (Epidermal Growth Factor Receptor) in this effect. Treatment of gingival fibroblasts with EMD resulted in tyrosine phosphorylation of the EGFR, as assessed by immunoblotting and ELISA, while EMD-induced ERK activation and thymidine incorporation were markedly inhibited (~ 40–50%) by a specific EGFR tyrosine kinase inhibitor. Using appropriate inhibitors, we established that EMD-induced EGFR activation is largely due to shedding of HB-EGF (Heparin-binding EGF) from the cell membrane via a metalloproteinase-mediated process. Finally, the addition of PP1, a Src family inhibitor, abrogated both EGFR phosphorylation and ERK activation. Taken together, these results indicate that, at least in human gingival fibroblasts, EMD-induced ERK activation and proliferation are partially due to a Src-dependent, metalloproteinase-mediated transactivation of EGFR.
Stereometric Assessment of TMJ Space Variation by Occlusal Splints
Authors: Ettlin D.A. , Mang H. , Colombo V. , Palla S. , Gallo L.M.
Published: January 2009

Occlusal splints are used for the management of temporomandibular disorders, although their mechanism of action remains controversial. This study investigated whether insertion of an occlusal splint leads to condyle-fossa distance changes, and to mandibular rotation and/or translation. By combining magnetic resonance images with jaw tracking (dynamic stereometry), we analyzed the intra-articular distances of 20 human temporomandibular joints (TMJs) before and after insertion of occlusal splints of 3 mm thickness in the first molar region. For habitual closure, protrusion, and laterotrusion in the contralateral joint, occlusal splints led to minor—yet statistically significant—increases of global TMJ space and to larger increases at defined condylar areas. Condylar end rotation and translation in habitual closure were reduced. Hence, the insertion of a 3-mm-thick occlusal splint led to a change in the topographical condyle-fossa relationship, and therefore to a new distribution of contact areas between joint surfaces.
Corticotomy-/Osteotomy-assisted Tooth Movement microCTs Differ
Authors: Lee W. , Karapetyan G. , Moats R. , Yamashita D.-D. , Moon H.-B. , Ferguson D.J. , Yen S.
Published: January 2009

Corticotomy-assisted and osteotomy-assisted tooth movement involves surgical incisions through the alveolar bone. To ascertain whether teeth move by distraction osteogenesis or by regional accelerated phenomenon (RAP), we randomly assigned 30 Sprague-Dawley rats to one of 5 experimental groups: corticotomy alone, corticotomy-assisted tooth movement, osteotomy alone, osteotomy-assisted tooth movement, or tooth movement alone. Each animal was imaged by microtomography immediately after surgery, after 21 days, and after 2 months. After 21 days, regional accelerated phenomenon was observed in the alveolar bone of the corticotomy-treated animals and distraction osteogenesis in the osteotomy-assisted tooth movement animals. Pixel count data were analyzed by nested ANOVA for 5 experimental groups, split-mouth controls, 3 levels along the root, and 5 sites per level. The most demineralized sites after 21 days differed for each of the experimental groups. Our study indicates that osteotomies and corticotomies induce different alveolar bone reactions, which can be exploited for tooth movement.
Matrix Gla Protein Inhibition of Tooth Mineralization
Authors: Kaipatur N.R. , Murshed M. , McKee M.D.
Published: January 2009

Extracellular matrix (ECM) mineralization is regulated by mineral ion availability, proteins, and other molecular determinants. To investigate protein regulation of mineralization in tooth dentin and cementum, and in alveolar bone, we expressed matrix Gla protein (MGP) ectopically in bones and teeth in mice, using an osteoblast/odontoblast-specific 2.3-kb Col1a1 promoter. Mandibles were analyzed by radiography, micro-computed tomography, light microscopy, histomorphometry, and transmission electron microscopy. While bone and tooth ECMs were established in the Col1a1-Mgp mice, extensive hypomineralization was observed, with values of unmineralized ECM from four- to eight-fold higher in dentin and alveolar bone when compared with that in wild-type tissues. Mineralization was virtually absent in tooth root dentin and cellular cementum, while crown dentin showed “breakthrough” areas of mineralization. Acellular cementum was lacking in Col1a1-Mgp teeth, and unmineralized osteodentin formed within the pulp. These results strengthen the view that bone and tooth mineralization is critically regulated by mineralization inhibitors.
A New Inflammatory Cytokine on the Block: Re-thinking Periodontal Disease and the Th1/Th2 Paradigm in the Context of Th17 Cells and IL-17
Authors: Gaffen S.L. , Hajishengallis G.
Published: January 2009

For almost two decades, the Th1/Th2 paradigm has offered a productive conceptual framework for investigating the pathogenesis of periodontitis. However, as with many other inflammatory diseases, the observed role of T-cell-mediated immunity in periodontitis did not readily fit this model. A new subset of CD4+ T-cells was recently discovered that explains many of the discrepancies in the classic Th1/Th2 model, and has been termed “Th17” based on its secretion of the novel pro-inflammatory cytokine IL-17. The identification of Th17 cells as a novel effector T-cell population compels re-examination of periodontitis in the context of the new subset and its signature cytokines. This review aims to offer a clarifying insight into periodontal pathogenesis under the extended Th1/Th2/Th17 paradigm, and is predicated on the principle that periodontal disease activity is determined by a complex interplay between the immune system and periodontal pathogens. The re-examination of existing periodontal literature and further studies in the light of these new discoveries may help explain how the inflammatory response results in damage to the periodontium while generally failing to control the pathogens. This knowledge is essential for the development of immunomodulatory intervention strategies for fine-tuning the host response to maximize the protective and minimize the destructive aspects of the periodontal host response. Moreover, with the advent of anti-cytokine biologic drugs that target the Th1 and Th17 pathways in autoimmunity, the potential consequences to periodontal disease susceptibility in humans need to be understood.
Tail Regeneration in Xenopus laevis as a Model for Understanding Tissue Repair
Authors: Tseng A.-S. , Levin M.
Published: January 2009

Augmentation of regenerative ability is a powerful strategy being pursued for the biomedical management of traumatic injury, cancer, and degeneration. While considerable attention has been focused on embryonic stem cells, it is clear that much remains to be learned about how somatic cells may be controlled in the adult organism. The tadpole of the frog Xenopus laevis is a powerful model system within which fundamental mechanisms of regeneration are being addressed. The tadpole tail contains spinal cord, muscle, vasculature, and other terminally differentiated cell types and can fully regenerate itself through tissue renewal—a process that is most relevant to mammalian healing. Recent insight into this process has uncovered fascinating molecular details of how a complex appendage senses injury and rapidly repairs the necessary morphology. Here, we review what is known about the chemical and bioelectric signals underlying this process and draw analogies to evolutionarily conserved pathways in other patterning systems. The understanding of this process is not only of fundamental interest for the evolutionary and cell biology of morphogenesis, but will also generate information that is crucial to the development of regenerative therapies for human tissues and organs.
Protein Antigen in Serotype k Streptococcus mutans Clinical Isolates
Authors: Nakano K. , Nomura R. , Nemoto H. , Lapirattanakul J. , Taniguchi N. , Grönroos L. , Alaluusua S. , Ooshima T.
Published: January 2009

Streptococcus mutans, a major pathogen of dental caries and infective endocarditis, is classified into serotypes c, e, f, and k, with serotype k strains recently reported to be frequently detected in persons with infective endocarditis. Thus, we hypothesized that common properties associated with infective endocarditis are present in those strains. Fifty-six oral S. mutans strains, including 11 serotype k strains, were analyzed. Western blotting analysis revealed expression of the 3 types of glucosyltransferases in all strains, while expression of the approximately 190-kDa cell-surface protein (PA) was absent in 12 strains, among which the prevalence of serotype k (7/12) was significantly high. Furthermore, cellular hydrophobicity and phagocytosis susceptibility were lower in the group of serotype k strains. These results indicate that the absence of PA expression, low cellular hydrophobicity, and phagocytosis susceptibility are common bacterial properties associated with serotype k strains, which may be associated with virulence for infective endocarditis.
Affluent Neighborhoods Reduce Excess Risk of Tooth Loss among the Poor
Authors: Sanders A.E. , Turrell G. , Slade G.D.
Published: January 2009

The effect of neighborhood on health may vary according to the characteristics of the residents. We tested the hypothesis that, in affluent neighborhoods, low-income adults retain more teeth than their income-equivalent peers in poor neighborhoods. In 2003, the Adelaide Small Area Dental Study collected sociodemographic and tooth retention information from 2860 adults in 60 neighborhoods. Neighborhood socio-economic position was a census-based composite measure. Using multilevel modelling, we fitted a series of two-level random intercept variance component models. Findings revealed significant main effects for individual and neighborhood predictors and a significant interaction between neighborhood disadvantage and low income. In affluent areas, disparities in tooth retention were negligible, but in poor neighborhoods, substantial variation in tooth retention between individuals was found based on their level of income. Low-income adults appeared to benefit from living in affluent areas, while wealthier adults living in poor neighborhoods did not lose their oral health advantage.
Neuropeptide Y Y1 Receptor Effects on Pulpal Nociceptors
Authors: Gibbs J.L. , Hargreaves K.M.
Published: January 2009

Neuropeptide Y (NPY) is an important modulatory neuropeptide that regulates several physiological systems, including the activity of sensory neurons. We evaluated whether activation of the NPY Y1 receptor could modulate the activity of capsaicin-sensitive nociceptors in trigeminal ganglia and dental pulp. We tested this hypothesis by measuring capsaicin-stimulated calcitonin gene-related peptide release (CGRP) as a measure of nociceptor activity. Capsaicin-evoked CGRP release was inhibited by 50% (p < 0.05) in trigeminal ganglia and by 26% (p < 0.05) in dental pulp when tissues were pre-treated with [Leu31,Pro34]NPY. The Y1 receptor was found to co-localize with the capsaicin receptor TRPV1 in trigeminal ganglia. These results demonstrate that activation of the Y1 receptor results in the inhibition of the activity of capsaicin-sensitive nociceptors in the trigeminal ganglia and dental pulp. These findings are relevant to the physiological modulation of dental nociceptors by endogenous NPY and demonstrate an important novel analgesic target for the treatment of dental pain.
Effects of Low-energy Shock Waves on Oral Bacteria
Authors: Novak K.F. , Govindaswami M. , Ebersole J.L. , Schaden W. , House N. , Novak M.J.
Published: January 2009

We have recently demonstrated that extracorporeal shock-wave therapy (ESWT) is effective in promoting the healing of dermal wounds and in regenerating alveolar bone lost through periodontal disease. The objective of the present study was to determine any antibacterial effect of ESWT on oral bacteria. Monoculture suspensions of 6 bacterial species were treated with 100 to 500 pulses of ESWT at energy flux densities (EFD) of 0.12 mJ/mm2, 0.22 mJ/mm2, and 0.3 mJ/mm2. Following treatment, aliquots were plated for viability determination and compared with untreated controls. ESWT showed a significant microbicidal effect for Streptococcus mutans and an unencapsulated strain of Porphyromonas gingivalis following as few as 100 pulses at 0.3 mJ/mm2 (p ≤ 0.001). In addition, a significant disruption of bacterial aggregates was observed at lower EFDs. No significant reduction in viability was observed for all other bacteria at EFDs and pulses tested (p > 0.05). These findings suggest that low-energy ESWT may be bactericidal for selected oral bacteria.
P. gingivalis Regulates the Expression of Cathepsin B and Cystatin C
Authors: Elkaim R. , Werner S. , Kocgozlu L. , Tenenbaum H.
Published: January 2009

Porphyromonas gingivalis is a major etiological agent of periodontitis that could affect the expression of Cathepsins B and C by disrupting the balance between these enzymes and their inhibitor, Cystatin C. We tested this hypothesis by infecting human oral epithelial cells with P. gingivalis or activating solely by its lipopolysaccharide. The mRNA level, the enzymatic activity, and the protein expression of Cathepsin B were increased (three-fold) in a dose-dependent manner, while those of Cystatin C decreased (five-fold). No changes were observed for Cathepsin C. Although activation by lipopolysaccharides led to a delayed imbalance (2 days) between Cathepsin B and Cystatin C, this imbalance took place very rapidly during the infection (< 6 hrs), indicating that the whole bacterium contains components that initiate rapid changes in the transcription rates of Cathepsin B and Cystatin C and selectively modify the molecular pathways that lead to this imbalance.
Direct and Indirect Effects of Interdental Hygiene in a Clinical Trial
Authors: Tu Y.-K. , Jackson M. , Kellett M. , Clerehugh V.
Published: January 2009

Many randomized controlled trials (RCTs) in dental research test the efficacy of interventions on more than one outcome variable. Univariate methods, such as the t test or analysis of covariance, cannot evaluate the efficacy of interventions on multiple outcomes simultaneously. The aim of this study was to use structural equation modeling (SEM) to re-analyze a RCT, comparing the effects of pre-curved interdental brushes and flossing on probing pocket depth (PPD), plaque indices, and bleeding on probing (BOP) measured at baseline, intermediate, and final examinations. Results of SEM showed that the observed greater reduction in PPD and BOP in persons using interdental brushing than in those flossing is due mainly to the greater efficiency in plaque removal with the interdental brushes (indirect effect) rather than to the compression of the interdental papillae (direct effect). In contrast, smokers showed less BOP at baseline but also less improvement in BOP through direct effects.
The Influence of Barrier Membranes on Autologous Bone Grafts
Authors: Gielkens P.F.M. , Schortinghuis J. , de Jong J.R. , Paans A.M.J. , Ruben J.L. , Raghoebar G.M. , Stegenga B. , Bos R.R.M.
Published: January 2009

In implant dentistry, there is continuing debate regarding whether a barrier membrane should be applied to cover autologous bone grafts in jaw augmentation. A membrane would prevent graft remodeling with resorption and enhance graft incorporation. We hypothesized that membrane coverage does not effect resorption and incorporation of autologous onlay bone grafts. We treated 192 male Sprague-Dawley rats. A 4.0-mm-diameter bone graft was harvested from the right mandibular angle and transplanted to the left. Poly(DL-lactide-ε-caprolactone), collagen, and expanded polytetrafluoroethylene membranes were used to cover the grafts. The controls were left uncovered. Graft resorption at 2, 4, and 12 weeks was evaluated by post mortem microradiography and microCT. Analysis of the data showed no significant differences among the 4 groups. This demonstrates that the indication of barrier membrane use, to prevent bone remodeling with resorption and to enhance incorporation of autologous onlay bone grafts, is at least disputable.
Mechanism of Azithromycin Treatment on Gingival Overgrowth
Authors: Kim J.-Y. , Park S.-H. , Cho K.-S. , Kim H.-J. , Lee C.-K. , Park K.-K. , Choi S.-H. , Chung W.-Y.
Published: January 2009

Azithromycin is effective for the remission of cyclosporine A-induced gingival overgrowth (CIGO) in persons who have undergone renal transplant. To explain its mechanism in alleviating the clinical symptoms of these indivduals, we examined the effect of azithromycin on cell proliferation and collagen turnover modified by cyclosporin A in human gingival fibroblasts from healthy persons and from persons who had undergone renal transplant. Cyclosporin A-induced proliferation of renal transplant fibroblasts and normal fibroblasts was inhibited by azithromycin. Azithromycin elevated the reduced metalloproteinase (MMP)-1 and MMP-2 activities in cyclosporine A-treated renal transplant fibroblasts and normal fibroblasts. In cyclosporine A-treated renal transplant fibroblasts, azithromycin blocked the accumulation of total collagen in culture media and the increase in type I collagen mRNA level, but recovered the reduced MMP-2 mRNA level to the control. These results suggest that azithromycin may improve CIGO by blocking cyclosporine A-induced cell proliferation and collagen synthesis, and by activating MMP-2 in gingival fibroblasts of persons with cyclosporine A-induced gingival overgrowth.
XBP1 May Determine the Size of the Ameloblast Endoplasmic Reticulum
Authors: Tsuchiya M. , Tye C.E. , Sharma R. , Smith C.E. , Bartlett J.D.
Published: January 2009

Ameloblasts progress through defined stages of development as enamel forms on teeth. Pre-secretory ameloblasts give rise to tall columnar secretory ameloblasts that direct the enamel to achieve its full thickness. During the maturation stage, the ameloblasts shorten and direct the enamel to achieve its final hardened form. Here we ask how the volume of selected ameloblast organelles changes (percent volume per ameloblast) as ameloblasts progress through six defined developmental stages. We demonstrate that mitochondria volume peaks during late maturation, indicating that maturation-stage ameloblasts maintain a high level of metabolic activity. Also, the endoplasmic reticulum (ER) volume changes significantly as a function of developmental stage. This prompted us to ask if X-box-binding protein-1 (XBP1) plays a role in regulating ameloblast ER volume, as has been previously demonstrated for secretory acinar cells and for plasma cell differentiation. We demonstrate that Xbp1 expression correlates positively with percent volume of ameloblast ER.
Association between High miR-211 microRNA Expression and the Poor Prognosis of Oral Carcinoma
Authors: Chang K.-W. , Liu C.-J. , Chu T.-H. , Cheng H.-W. , Hung P.-S. , Hu W.-Y. , Lin S.-C.
Published: January 2009

MicroRNAs (miRNAs) are non-coding RNAs that play roles in gene silencing and may be involved in tumorigenesis. miR-211 was mapped to chromosome 15q13, a locus frequently altered in cancers. The role of miR-211in carcinogenesis has not been clearly defined, however. This study investigated the pathogenetic implications of miR-211 in oral carcinogenesis. An association was found between higher miR-211 expression and the most advanced nodal metastasis, vascular invasion, and poor prognosis of oral carcinoma. The function of enforced miR-211 expression in oral carcinoma cells was confirmed by the repression of LacZ in a reporter plasmid via miR-211 targeting. Enforced miR-211 expression significantly increased the proliferation, migration, and anchorage-independent colony formation of oral carcinoma cells, while it enhanced the tumorigenicity of only SAS high-grade oral carcinoma cells, but not OECM-1 non-tumorigenic cells. The findings suggest that high miR-211 expression may be associated with the progression of oral carcinoma and poor patient outcomes.
Time-dependent Activation of ERK1/2 in Nerve Terminals of the Dentin-Pulp Complex following Bradykinin Treatment
Authors: Korkmaz Y. , Bloch W. , Schneider K. , Zimmer S. , Addicks K. , Raab W.H.-M.
Published: January 2009

The extracellular signal-regulated kinases 1 and 2 (ERK1/2) have been implicated in the inflammation-dependent sensitization of nociceptors, and the inflammatory mediator bradykinin (BK) led to a reduced threshold in the nociceptor terminals, activating intracellular signaling by phosphorylating receptors and ion channels. The effects of BK on the non-transcriptional modulation of the ERK1/2 in the peripheral nociceptor terminals, including in nerve endings of the dentin-pulp complex, are unknown. The time-dependent effects of BK (10−7M) on the ERK1/2 phosphorylation in nerve terminals of the dentin-pulp complex were investigated by quantitative and double immunolabeling with organ bath experiments. In nerve terminals, total and p-ERK1/2 were detected. In comparison with the controls, the numbers of p-ERK1/2-positive nerve endings increased after 1 and 3 min and decreased after 10 min of BK treatment. Analysis of the data indicates that BK induces phosphorylation-mediated local activation of ERK1/2 in nerve terminals modulating nociception in the dentin-pulp complex.
Phenotypic Heterogeneity of Streptococcus mutans in Dentin
Authors: Rupf S. , Hannig M. , Breitung K. , Schellenberger W. , Eschrich K. , Remmerbach T. , Kneist S.
Published: January 2009

Information concerning phenotypic heterogeneity of Streptococcus mutans in carious dentin is sparse. Matrix-assisted laser-desorption/ionization-time-of-flight mass-spectrometry (MALDI-TOF-MS) facilitates the phenotypic differentiation of bacteria to the subspecies level. To verify a supposed influence of restorative treatment on the phenotypic heterogeneity of S. mutans, we isolated and compared a total of 222 S. mutans strains from dentin samples of 21 human deciduous molars during caries excavation (T1) and 8 wks (T2) after removal of the temporary restoration. Phenotypic heterogeneity was determined by MALDI-TOF-MS and hierarchical clustering. Thirty-six distinct S. mutans phenotypes could be identified. Although indistinguishable phenotypes were found in the same teeth at T1 and T2, as well as in different teeth of individual participants, the phenotypic heterogeneity increased significantly, from 1.4 phenotypes per S. mutans-positive dentin sample at T1 to 2.2 phenotypes at T2. We attribute this to an adaptation of S. mutans to the modified environment under the restoration following caries excavation.
Effects of VEGF and FGF2 on the Revascularization of Severed Human Dental Pulps
Authors: Mullane E.M. , Dong Z. , Sedgley C.M. , Hu J.C.-C. , Botero T.M. , Holland G.R. , Nör J.E.
Published: January 2009

The long-term outcome of replanted avulsed permanent teeth is frequently compromised by lack of revascularization, resulting in pulp necrosis. The purpose of this study was to evaluate the effects of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF-2) on the revascularization of severed human dental pulps. Tooth slices were prepared from non-carious human molars and treated with 0–50 ng/mL rhVEGF165 or rhFGF-2 for 7 days in vitro. Both angiogenic factors enhanced pulp microvessel density compared with untreated controls (p < 0.05). Tooth slices were also treated with 0 or 50 ng/mL rhVEGF165 for one hour prior to implantation into the subcutaneous space of immunodeficient mice. Treatment with rhVEGF165 increased pulp microvessel density in vivo (p < 0.05). These results demonstrate that rhVEGF165 enhanced neovascularization of severed human dental pulps and suggest that topical application of an angiogenic factor prior to replantation might be beneficial for the treatment of avulsed teeth.
Orally Based Diagnosis of Celiac Disease: Current Perspectives
Authors: Pastore L. , Campisi G. , Compilato D. , Muzio L. Lo
Published: January 2009

Celiac disease (CD) is a lifelong immune-mediated disorder caused by the ingestion of wheat gluten in genetically susceptible persons. Most cases of CD are atypical and remain undiagnosed, which exposes the individuals to the risk of life-threatening complications. Serologic endomysial and tissue transglutaminase antibody tests are used to screen at-risk individuals, although a firm diagnosis requires demonstration of characteristic histopathologic findings in the small-intestinal mucosa. A gluten challenge, with a repeat biopsy to demonstrate recurrence of histopathologic changes in the intestinal mucosa after the re-introduction of gluten, is considered for those persons in whom diagnosis remains in doubt. In this paper, we review studies that evaluated: (1) the possibility of using oral mucosa for the initial diagnosis of CD or for local gluten challenge; and (2) the possibility of using salivary CD-associated antibodies as screening tests. Our review shows that orally based diagnosis of CD is attractive and promising, although additional evaluations with standardized collection and analysis methods are needed. There is some evidence of a dissociation between systemic and oral mucosal immune responses in CD. The hypothesis that gluten could stimulate naïve lymphocytes directly in the oral cavity would have important implications for the understanding, diagnosis, and management of CD.
Damage Maps of Veneered Zirconia under Simulated Mastication
Authors: Kim J.-W. , Kim J.-H. , Janal M.N. , Zhang Y.
Published: January 2009

Zirconia-based restorations often fracture from chipping and/or delamination of the porcelain veneers. We hypothesized that veneer chipping/delamination is a result of the propagation of near-contact-induced partial cone cracks on the occlusal surface under mastication. Masticatory loading involves the opposing tooth sliding along the cuspal inner incline surface with an applied biting force. To test this hypothesis, we cemented flat porcelain-veneered zirconia plates onto dental composites and cyclically loaded them (contact–slide–liftoff) at an inclination angle as a simplified model of zirconia-based restorations under occlusion. In light of in situ observation of damage evolution in a transparent glass/zirconia/polycarbonate trilayer, post mortem damage evaluation of porcelain/zirconia/composite trilayers by a sectioning technique revealed that deep-penetrating occlusal surface partial cone fracture is the predominant fracture mode of porcelain veneers. Clinical relevance is discussed.