Odontogenesis

Although the precise mechanisms of the conversion of predentin to dentin are not well understood, several lines of evidence implicate the noncollagenous proteins (NCPs) as important regulators of dentin biomineralization. Here we compared the in vivo temporospatial expression patterns of two dentin NCP genes, dentin matrix protein 1 (Dmp1), and dentin sialophosphoprotein (DSPP) in developing molars. Reverse transcription-polymerase chain reaction was performed on embryonic day 13 to 1-day-old first molars using Dmp1- and DSPP-specific primer sets. Dmp1 transcripts appeared at the late bud stage, while DSPP mRNA was seen at the cap stage. Expression of both genes was sustained throughout odontogenesis. In situ hybridization analysis revealed interesting differences in the expression patterns of these genes. While Dmp1 and DSPP showed coexpression in young odontoblasts before the start of mineralization, the expression of these genes was notably distinct at later stages. Dmp1 expression decreased in secretory odontoblasts after the appearance of mineral, while high levels of DSPP were sustained in odontoblasts. In early secretory ameloblasts, DSPP expression was transient and down-regulated with the appearance of dentin matrix. Interestingly, Dmp1 expression became evident in ameloblasts during the maturative phase of amelogenesis. In contrast to Dspp expression that was tooth-specific, Dmp1 was expressed by osteoblasts throughout ossification in the skeleton. Probes directed to the “DSP” and “DPP” regions of the DSPP gene showed identical patterns of mRNA expression. These data show that the developmental expression patterns of Dmp1 and DSPP are distinct, implying that these molecules serve different biological functions in vivo.

The debate about the origin of the vertebrate dentition has been given fresh fuel by new fossil discoveries and developmental studies of extant animals. Odontodes (teeth or tooth-like structures) can be found in two distinct regions, the 'internal' oropharyngeal cavity and the 'external' skin. A recent hypothesis argues that regularly patterned odontodes is a specific oropharyngeal feature, whereas odontodes in the external skeleton lack this organization. However, this argument relies on the skeletal system of modern chondrichthyans (sharks and their relatives), which differ from other gnathostome (jawed vertebrate) groups in not having dermal bones associated with the odontodes. Their external skeleton is also composed of monoodontode 'placoid scales', whereas the scales of most early fossil gnathostomes are polyodontode, i.e. constructed from several odontodes on a shared bony base. Propagation phase contrast X-ray Synchrotron microtomography (PPC-SRmCT) is used to study the polyodontode scales of the early bony fish Andreolepis hedei. The odontodes constructing a single scale are reconstructed in 3D, and a linear and regular growth mechanism similar to that in a gnathostome dentition is confirmed, together with a second, gap-filling growth mechanism. Acanthodian tooth whorls are described, which show that ossification of the whorl base preceded and probably patterned the development of the dental lamina, in contrast to the condition in sharks where the dental lamina develops early and patterns the dentition.The new findings reveal, for the first time, how polyodontode scales grow in 3D in an extinct bony fish. They show that dentition-like odontode patterning occurs on scales and that the primary patterning unit of a tooth whorl may be the bony base rather than the odontodes it carries. These results contradict the hypothesis that oropharyngeal and external odontode skeletons are fundamentally separate and suggest that the importance of dermal bone interactions to odontode patterning has been underestimated.

Biomimicry has been introduced as a term for innovations inspired by nature [1]. Such innovations may appear in almost every part of modern society. This review on the effects of enamel matrix proteins on the formation of cementum and the development of emdogain for regeneration of periodontal tissues lost due to periodontitis shows an example of biomimicry in dentistry. Findings from clinical and laboratory investigations are summarized and the biological basis for enamel matrix-induced periodontal regeneration is discussed.

Introduction: True regeneration of the dental pulpdentin complex in immature teeth with necrotic pulps has not been shown histologically. It is not known to what extent this true tissue regeneration is necessary to achieve clinically acceptable outcomes. Methods: This case report describes the treatment of a patient with an immature maxillary right central incisor with a history of impact trauma and enamel-dentin crown fracture. A diagnosis of pulp necrosis with acute apical abscess was established. A regenerative endodontic protocol that used a paste containing Augmentin for 5 weeks as an intracanal medicament was used. Results: Follow-ups at 9, 12, 17, and 31 months revealed complete osseous healing of the periapical lesion and formation of the root apex, but without increase in root length. Clinically, the tooth was functional, asymptomatic, and nonresponsive to pulp vitality tests. The crown discolored over time. On reentering the root canal, no tissues were observed under magnification inside the root canal space. The root canal treatment was completed with mineral trioxide aggregate obturation. Conclusions: Augmentin might be an acceptable choice for root canal disinfection in regenerative endodontic procedures. The protocol for regenerative endodontic treatment is not predictable for pulp-dentin regeneration. Formation of the root apex is possible without pulp regeneration. (J Endod 2013;39:1291-1295

Objectives: The purpose of this review, commissioned by the Administration for Children and Families, the Health Resources and Services Administration, the Health Care Financing Administration, and the Department of Agriculture's Food and Nutrition Service, was to update the evidence of the dietary factors that affect dental caries, and subsequently formulate dietary recommendations for preschool children based on principles of cariology. Methods: Literature on the dental caries process, dietary factors affecting dental caries initiation and progression, and nutrition education and counseling were reviewed and synthesized. Dietary guidelines for children at various ages were then constructed based on the review. Results: Dental caries in preschool children is due to a combination of factors, including colonization of teeth with cariogenic bacteria, type of foods and frequency of exposure of these foods to the cariogenic bacteria, and susceptible teeth. Caries risk is greatest if sugars are consumed at high frequency and are in a form that is retained in the mouth for long periods. Sucrose is the most cariogenic sugar because it can form glucan that enables firm bacterial adhesion to teeth and

RESUMEN: La anestesia local odontológica es un procedimiento de rutina en la práctica odontológica pediátrica que, tal como otros sucesos, podría generar anomalías en el desarrollo dental, considerando la susceptibilidad de los gérmenes dentales en desarrollo; por lo anterior consideramos necesario determinar la existencia de asociación entre anomalías del desarrollo dental y el uso de técnicas anestésicas. Para esto se diseñó un estudio descriptivo basado en búsqueda sistemática de literatura en las bases de datos: Scopus, MEDLINE, Web of Science Core Collection, ProQuest Central, Korean Journal Database y SciELO, utilizando combinación de términos MeSH: ("odontoblasts" OR "ameloblasts" OR "odontogenesis" OR "amelogenesis" OR "dentinogenesis" OR "odontodysplasia" OR "dental enamel hypoplasia" OR "dental sac" OR "dental papilla" OR "enamel organ") AND ("anesthesia" OR "local anesthesia" OR "nerve block" OR "dental anesthesia"). De un total de 96 artículos, se incluyeron para revisión 5 artículos relacionados con los objetivos de esta revisión, excluyéndose las coincidencias. La evidencia presente en la literatura es contradictoria. Existen múltiples diferencias entre los estudios analizados, las que podrían deberse a las técnicas anestésicas involucradas, tipo de anestésico, la no consideración de otros posibles agentes causales (síndromes) o la terapia odontológica. No puede ser determinado una relación entre estos dos aspectos.

PALABRAS CLAVE: anestesia dental, desarrollo dental, anomalías.

ABSTRACT: The dental local anesthesia is a routine procedure in pediatric dental practice that, as other events could generate abnormalities in dental development, considering the susceptibility of developing tooth germs. From the foregoing it necessary to determine the existence of association between disorders of tooth development and use of anesthetic techniques. A descriptive study based on systematic literature review in databases: Scopus, MEDLINE, Web of Science Core Collection, ProQuest Central, Korean Journal Database and SciELO data was designed, using the following combination of MeSH terms ("odontoblasts" OR "ameloblasts" OR "odontogenesis" OR "amelogenesis" OR "dentinogenesis" OR "odontodysplasia" OR "dental enamel hypoplasia" OR "dental sac" OR "dental papilla" OR "enamel organ") AND ("anesthesia" OR "local anesthesia "OR" nerve block "OR" dental anesthesia"). A total of 96 articles, were included for review a total of 5 articles related to the objectives of this review, excluding the matches. The present evidence in the literature is contradictory. There are many differences between the studies analyzed, which could be due to the anesthetic techniques involved, type of anesthetic, other possible causative agents (syndromes) or dental treatment are not included. It can not be determined a relationship between these two aspects.

KEY WORDS: dental anesthesia, dental development, abnormalities.

Introduction: In this research project, we aimed to compare the effectiveness of single (1 deciduous canine) and double (deciduous canine and first molar) extractions in subjects with retained maxillary permanent canines positioned palatally or centrally in the alveolar crest, at risk for root resorption of adjacent permanent teeth. Methods: Subjects at risk for canine impaction or resorptive situations were randomly assigned to 1 of 2 treatment modalities: single extraction (17 patients, 28 canines) or double extraction (20 patients, 37 canines). Thirty-one patients with 53 canines judged to be not at risk constituted the untreated control group. Panoramic radiographs were taken at the initial observation and after 18 months on average. Between-group statistical comparisons were carried out on the changes in canine inclination and sector location (measured on panoramic radiographs) and on the percentages of successful permanent canine eruptions. Results: The double-extraction group showed significant improvements in the success rate and the intrabony position of the permanent canine, in terms of uprighting the canine's long axis with a crown movement in a distal direction. Conclusions: Concomitant deciduous canine and first molar extractions proved to be more effective as a preventive approach to promote eruption of retained maxillary permanent canines positioned palatally or centrally. (Am J Orthod Dentofacial Orthop 2011;139:316-23)

The contemporary treatment of cleft lip and palate involves a sequence of surgical procedures and orthodontic management. Alveolar bone grafting (ABG) is usually undertaken after orthodontic expansion of the maxillary segments between the ages of eight and 12 years. Two of the important goals of alveolar bone grafting are the provision of bony support for the eruption of the canine and the closure of residual oro-nasal fistulae. The purpose of this study was to retrospectively evaluate the root development and eruption of the canine following ABG. Methods: Group 1: radiographic and clinical records of a sample of 19 cleft patients who underwent alveolar bone grafting procedures, performed between 1996 and 1999 were reviewed. Group 2: a random sample of 15 cleft patients attending for routine dental review were clinically examined. The age of patient, degree of root development and eruption status of the canine, and presence of oronasal fistulae pre and post alveolar bone grafting were evaluated. Results: Most cleft canines had continued root development and descended in the alveolus towards eruption following ABG. Four canine teeth (8 per cent) were impacted and required surgical exposure and orthodontic treatment following failure of eruption. Closure of anterior oro-nasal fistulae at the time of grafting was maintained post-operatively. Conclusions: This study demonstrated that canine root development and eruption continued satisfactorily through grafted alveolar clefts in most cases and closure of anterior oro-nasal fistulae was achieved in all cases.

The study was undertaken to evaluate mineral trioxide aggregate (MTA) clinically and radiographically as a pulpotomy agent in immature permanent teeth whose pulps were exposed by a complicated crown fracture. Thirty incisors with exposed pulps in twenty-nine patients were examined for this retrospective study. According to exclusion criteria, only twenty-seven teeth were selected. Each tooth was treated with partial pulpotomy and the wounded pulp was covered with mineral trioxide aggregate. The children were recalled for clinical and radiographic evaluation at 3 months, 6 months, at approximately 12 months and 36 months. Out of 27 cases, 22 were categorized as 'healed' and 1 as 'healing'. The remaining 4 ones highlighted persistent disease and needed further endodontic treatment. MTA partial pulpotomy is an effective treatment in maintaining pulpal vitality and allowing physiological root development (apexogenesis).

Keratoameloblastoma (KA) is a rare histological variant of the ameloblastoma with extensive
keratin production within the odontogenic islands as well as in the fbrous stroma. Pindborg frst reported it
in 1970, since then only 18 cases have been reported in the literature. We report a soft tissue recurrence of
KA, involving right posterior region of the lower jaw in a 27-year-old female.

Essentially we show recent data to shed new light on the thorny controversy of how teeth arose in evolution. Essentially we show (a) how teeth can form equally from any epithelium, be it endoderm, ectoderm or a combination of the two and (b) that the gene expression programs of oral versus pharyngeal teeth are remarkably similar. Classic theories suggest that (i) skin denticles evolved first and odontode-inductive surface ectoderm merged inside the oral cavity to form teeth (the 'outside-in' hypothesis) or that (ii) patterned odontodes evolved first from endoderm deep inside the pharyngeal cavity (the 'inside-out' hypothesis). We propose a new perspective that views odontodes as structures sharing a deep molecular homology, united by sets of co-expressed genes defining a competent thickened epithelium and a collaborative neural crest-derived ectomesenchyme. Simply put, odontodes develop 'inside and out', wherever and whenever these co-expressed gene sets signal to one another. Our perspective complements the classic theories and highlights an agenda for specific experimental manipulations in model and non-model organisms.

Data from living and extinct faunas of primitive vertebrates imply very different scenarios for the origin and evolution of the dermal and oral skeletal developmental system. A direct reading of the evolutionary relationships of living primitive vertebrates implies that the dermal scales, teeth, and jaws arose synchronously with a cohort of other characters that could be considered unique to jawed vertebrates: the dermoskeleton is primitively composed of numerous scales, each derived from an individual dental papilla; teeth are primitively patterned such that they are replaced in a classical conveyor-belt system. The paleontological record provides a unique but complementary perspective in that: 1) the organisms in which the skeletal system evolved are extinct and we have no recourse but to fossils if we aim to address this problem; 2) extinct organisms can be classified among, and in the same way as, living relatives; 3) a holistic approach to the incorporation of all data provides a more complete perspective on early vertebrate evolution. This combined approach is of no greater significance than in dealing with the origin of the skeleton and, combined with recent discoveries and new phylogenetic analyses, we have been able to test and reject existing hypotheses for the origin of the skeleton and erect a new model in their place.

The transcription factor Ctip2/Bcl11b plays essential roles in developmental processes of the immune and central nervous systems and skin. Here we show that Ctip2 also plays a key role in tooth development. Ctip2 is highly expressed in the ectodermal components of the developing tooth, including inner and outer enamel epithelia, stellate reticulum, stratum intermedium, and the ameloblast cell lineage. In Ctip2 ؊/؊ mice, tooth morphogenesis appeared to proceed normally through the cap stage but developed multiple defects at the bell stage. Mutant incisors and molars were reduced in size and exhibited hypoplasticity of the stellate reticulum. An ameloblast-like cell population developed ectopically on the lingual aspect of mutant lower incisors, and the morphology, polarization, and adhesion properties of ameloblasts on the labial side of these teeth were severely disrupted. Perturbations of gene expression were also observed in the mandible of Ctip2 ؊/؊ mice: expression of the ameloblast markers amelogenin, ameloblastin, and enamelin was down-regulated, as was expression of Msx2 and epiprofin, transcription factors implicated in the tooth development and ameloblast differentiation. These results suggest that Ctip2 functions as a critical regulator of epithelial cell fate and differentiation during tooth morphogenesis.

Mammalian tooth development is largely dependent on sequential and reciprocal epithelial-mesenchymal interactions. These processes involve a series of inductive and permissive interactions that result in the determination, differentiation, and organization of odontogenic tissues. Multiple signaling molecules, including BMPs, FGFs, Shh, and Wnt proteins, have been implicated in mediating these tissue interactions. Transcription factors participate in epithelial-mesenchymal interactions via linking the signaling loops between tissue layers by responding to inductive signals and regulating the expression of other signaling molecules. Adult stem cells are highly plastic and multipotent. These cells including dental pulp stem cells and bone marrow stromal cells could be reprogrammed into odontogenic fate and participated in tooth formation. Recent progress in the studies of molecular basis of tooth development, adult stem cell biology, and regeneration will provide fundamental knowledge for the realization of human tooth regeneration in the near future.

Carious pulp exposure in permanent molars of children is a common incident. Mineral trioxide aggregate is a new material that possesses numerous exciting possibilities for pulp therapy. Aim: The purpose of this study was to evaluate the efficiency of MTA as a direct pulp capping agent in young permanent teeth. Methods: Thirty asymptomatic permanent molars with pulp exposures were treated by pulp capping using MTA. At each recall (6, 12, 18 and 24 months), the teeth were assessed clinically, through pulpal sensitivity tests, as well as radiographically to evaluate periapical healing. Results: None of the cases reported spontaneous pain at the six months follow up and the pulp showed signs of vitality and absence of periapical radiolucency. At 24 months, the clinical and radiographic success rate was 93% with evidence of continued root growth. Conclusion: Pulp capping with MTA is recommended for teeth with carious pulp exposures specially immature teeth with high potential for healing.

Andreasen JO, Bakland LK, Andreasen FM. Traumatic intrusion of permanent teeth. Part 3. A clinical study of the effect of treatment variables such as treatment delay, method of repositioning, type of splint, length of splinting and antibiotics on 140 teeth. Ó Blackwell Munksgaard, 2006.

Teeth arise from sequential and reciprocal interactions between the oral epithelium and the underlying cranial neural crest-derived mesenchyme. Their formation involves a precisely orchestrated series of molecular and morphogenetic events, and gives us the opportunity to discover and understand the nature of the signals that direct cell fates and patterning. For that reason, it is important to elucidate how signaling factors work together in a defined number of cells to generate the diverse and precise patterned structures of the mature functional teeth. Over the last decade, substantial research efforts have been directed toward elucidating the molecular mechanisms that control cell fate decisions during tooth development. These efforts have contributed toward the increased knowledge on dental stem cells, and observation of the molecular similarities that exist between tooth development and regeneration.

Elucidation of the mechanisms controlling early development and organogenesis is currently progressing in several model species and a new field of research, evolutionary developmental biology, which integrates developmental and comparative approaches, has emerged. Although the expression pattern of many genes during tooth development in mammals is known, data on other lineages are virtually non-existent. Comparison of tooth development, and particularly of gene expression (and function) during tooth morphogenesis and differentiation, in representative species of various vertebrate lineages is a prerequisite to understand what makes one tooth different from another. Amphibians appear to be good candidates for such research for several reasons: tooth structure is similar to that in mammals, teeth are renewed continuously during life ( ¼ polyphyodonty), some species are easy to breed in the laboratory, and a large amount of morphological data are already available on diverse aspects of tooth biology in various species. The aim of this review is to evaluate current knowledge on amphibian teeth, principally concerning tooth development and replacement (including resorption), and changes in morphology and structure during ontogeny and metamorphosis. Throughout this review we highlight important questions which remain to be answered and that could be addressed using comparative morphological studies and molecular techniques. We illustrate several aspects of amphibian tooth biology using data obtained for the caudate Pleurodeles waltl. This salamander has been used extensively in experimental embryology research during the past century and appears to be one of the most favourable amphibian species to use as a model in studies of tooth development.

Adenomatoid odontogenic tumor (AOT) is an uncommon benign odontogenic tumor representing approximately 3% of all odontogenic tumors. In about 74% of cases, this tumor is associated with an impacted tooth, of which two-third of the cases is in relation to the maxillary anterior tooth. Rarely, this lesion can also occur in the absence of an impacted tooth within jaw bones. These variants of AOT are referred as extra follicular AOT. As the clinical picture and radiographic picture varies from the conventional AOT, the diagnosis is often challenging. Here, we report a case of extra follicular AOT of the anterior maxilla in a 22-year-old female patient.

Background: Although the predominant beneficial effect of fluoride occurs locally in the mouth, the adverse effect, dental fluorosis, occurs by the systemic route. The caries attack rate in industrializedcountries, including the Unitedstates and Canada, has decreased dramatically over the past 40 years. However, the prevalence of dental fluorosis in the United States has increased during the last 30 years both in communities with fluoridated water and in communities with nonfluoridated water. Dental fluorosis is closely associated with fluoride intake during the period of tooth development. Methods: We reviewed the major changes in infant feeding practices that have occurred since 1930 and the changes in fluoride intakes by infants and young children associated with changes in feeding practices. Results and Conclusions: Based on this review, we conclude that fluoride intakes of infants and children have shown a rather steady increase since 1930, are likely to continue to increase, and will be associated with further increase in the prevalence of enamel fluorosis unless intervention measures are instituted. Recommendations: We believe the most important measures that should be undertaken are ( I ) use, when feasible, of water low in fluoride for dilution of infant formulas; (2) adult supervision of toothbrushing by children younger than 5 years of age; and (3) changes in recommendations for administration of fluoride supplements so that such supplements are not given to infants and more stringent criteria are applied for administration to children.

Purpose: The purpose of this study was to compare mineral trioxide aggregate (MTA) with calcium hydroxide (Ca(OH)2) clinically and radiographically as a pulpotomy agent in immature permanent teeth (apexogenesis). Methods: Fifteen children, each with at least 2 immature permanent teeth requiring pulp- otomy (apexogenesis), were selected for this study. All selected teeth were evenly divided into 2 test groups. In

Oral submucous fibrosis (OSF) is a chronic, progressive, potentially malignant condition affecting the oral cavity
and frequently involving the upper part of the aerodigestive tract including the oropharynx and the upper part
of the esophagus. It is characterized by juxtaepithelial inflammatory reaction and progressive fibrosis of lamina
propria, leading to stiffening of the oral mucosa eventually causing trismus. This condition is associated with
significant morbidity and high risk of malignancy. Over the years, several drugs and combinations have been
tried for the treatment of submucous fibrosis, but with limited success, because of its unclear molecular
pathogenesis. Till date, there are no known effective treatments for OSF. The aim of this article is to emphasize
on the molecular changes taking place in OSF and possible therapeutic interventions

This review deals with the following seven aspects of vertebrate skeletogenic and odontogenic tissues.1The evolutionary sequence in which the tissues appeared amongst the lower craniate taxa.2The topographic association between skeletal (cartilage, bone) and dental (dentine, cement, enamel) tissues in the oldest vertebrates of each major taxon.3The separate developmental origin of the exo- and endoskeletons.4The neural-crest origin of cranial skeletogenic and odontogenic tissues in extant vertebrates.5The neural-crest origin of trunk dermal skeletogenic and odontogenic tissues in extant vertebrates.6The developmental processes that control differentiation of skeletogenic and odontogenic tissues in extant vertebrates.7Maintenance of developmental interactions regulating skeletogenic/odontogenic differentiation across vertebrate taxa. We derive twelve postulates, eight relating to the earliest vertebrate skeletogenic and odontogenic tissues and four relating to the development of these tissues in extant vertebrates and extrapolate the developmental data back to the evolutionary origin of vertebrate skeletogenic and odontogenic tissues. The conclusions that we draw from this analysis are as follows.8The dermal exoskeleton of thelodonts, heterostracans and osteostracans consisted of dentine, attachment tissue (cement or bone), and bone.9Cartilage (unmineralized) can be inferred to have been present in heterostracans and osteostracans, and globular mineralized cartilage was present in Eriptychius, an early Middle Ordovician vertebrate unassigned to any established group, but assumed to be a stem agnathan.10Enamel and possibly also enameloid was present in some early agnathans of uncertain affinities. The majority of dentine tubercles were bare.11The contemporaneous appearance of cellular and acellular bone in heterostracans and osteostracans during the Ordovician provides no clue as to whether one is more primitive than the other.12We interpret aspidin as being developmentally related to the odontogenic attachment tissues, either closer to dentine or a form of cement, rather than as derived from bone.13Dentine is present in the stratigraphically oldest (Cambrian) assumed vertebrate fossils, at present some only included as Problematica, and is cladistically primitive, relative to bone.14The first vertebrate exoskeletal skeletogenic ability was expressed as denticles of dentine.15Dentine, the bone of attachment associated with dentine, the basal bone to which dermal denticles are fused and cartilage of the Ordovician agnathan dermal exoskeleton were all derived from the neural crest and not from mesoderm. Therefore the earliest vertebrate skeletogenic/odontogenic tissues were of neural-crest origin.16Given the separate developmental and evolutionary origin of the cranial exo- and endoskeletons (both derivatives of the cranial neural crest) we conclude that bone (of attachment) was the primary skeletogenic tissue in the exoskeleton (cartilage being secondary), but that uncalcified cartilage was the primary skeletogenic tissue in the endoskeleton (bone – perichondral – being secondary).17Using evidence from developmental biology we conclude that the trunk neural crest of Ordovician agnathans was odontogenic, forming both dentine and bone of attachment of the trunk dermal exoskeleton.18Initiation of differentiation of skeletogenic and odontogenic tissues is controlled epigenetically by one or more epithelial-mesenchymal interactions in epigenetic cascades.19Changes in timing of steps in these epigenetic cascades provides an evolutionary mechanism for altering the types of skeletogenic/odontogenic tissues and/or structures formed.20The appearance of epithelial-mesenchymal interactions and the origin of the skeletogenic/odontogenic neural crest at the outset of vertebrate evolution provided the developmental basis for the evolutionary origin of vertebrate skeletogenic and odontogenic tissues and for the appearance and evolution of the vertebrate skeleton.The evolutionary sequence in which the tissues appeared amongst the lower craniate taxa.The topographic association between skeletal (cartilage, bone) and dental (dentine, cement, enamel) tissues in the oldest vertebrates of each major taxon.The separate developmental origin of the exo- and endoskeletons.The neural-crest origin of cranial skeletogenic and odontogenic tissues in extant vertebrates.The neural-crest origin of trunk dermal skeletogenic and odontogenic tissues in extant vertebrates.The developmental processes that control differentiation of skeletogenic and odontogenic tissues in extant vertebrates.Maintenance of developmental interactions regulating skeletogenic/odontogenic differentiation across vertebrate taxa. We derive twelve postulates, eight relating to the earliest vertebrate skeletogenic and odontogenic tissues and four relating to the development of these tissues in extant vertebrates and extrapolate the developmental data back to the evolutionary origin of vertebrate skeletogenic and odontogenic tissues. The conclusions that we draw from this analysis are as follows.The dermal exoskeleton of thelodonts, heterostracans and osteostracans consisted of dentine, attachment tissue (cement or bone), and bone.Cartilage (unmineralized) can be inferred to have been present in heterostracans and osteostracans, and globular mineralized cartilage was present in Eriptychius, an early Middle Ordovician vertebrate unassigned to any established group, but assumed to be a stem agnathan.Enamel and possibly also enameloid was present in some early agnathans of uncertain affinities. The majority of dentine tubercles were bare.The contemporaneous appearance of cellular and acellular bone in heterostracans and osteostracans during the Ordovician provides no clue as to whether one is more primitive than the other.We interpret aspidin as being developmentally related to the odontogenic attachment tissues, either closer to dentine or a form of cement, rather than as derived from bone.Dentine is present in the stratigraphically oldest (Cambrian) assumed vertebrate fossils, at present some only included as Problematica, and is cladistically primitive, relative to bone.The first vertebrate exoskeletal skeletogenic ability was expressed as denticles of dentine.Dentine, the bone of attachment associated with dentine, the basal bone to which dermal denticles are fused and cartilage of the Ordovician agnathan dermal exoskeleton were all derived from the neural crest and not from mesoderm. Therefore the earliest vertebrate skeletogenic/odontogenic tissues were of neural-crest origin.Given the separate developmental and evolutionary origin of the cranial exo- and endoskeletons (both derivatives of the cranial neural crest) we conclude that bone (of attachment) was the primary skeletogenic tissue in the exoskeleton (cartilage being secondary), but that uncalcified cartilage was the primary skeletogenic tissue in the endoskeleton (bone – perichondral – being secondary).Using evidence from developmental biology we conclude that the trunk neural crest of Ordovician agnathans was odontogenic, forming both dentine and bone of attachment of the trunk dermal exoskeleton.Initiation of differentiation of skeletogenic and odontogenic tissues is controlled epigenetically by one or more epithelial-mesenchymal interactions in epigenetic cascades.Changes in timing of steps in these epigenetic cascades provides an evolutionary mechanism for altering the types of skeletogenic/odontogenic tissues and/or structures formed.The appearance of epithelial-mesenchymal interactions and the origin of the skeletogenic/odontogenic neural crest at the outset of vertebrate evolution provided the developmental basis for the evolutionary origin of vertebrate skeletogenic and odontogenic tissues and for the appearance and evolution of the vertebrate skeleton.

Several growth factors and extracellular matrix molecules, which are expressed during embryonic tooth development, are re-expressed in dental tissues under pathological conditions. Pathological conditions such as caries lesions and dental injuries are often lethal to the odontoblasts, which are then replaced by other pulp cells. These cells are able to differentiate into odontoblast-like cells and produce a reparative dentin. Here we demonstrate the in vivo distribution of several molecules in human permanent teeth under normal and pathological conditions. The intermediate filament protein nestin, which is a marker of young odontoblasts, is absent from old permanent teeth. Similarly, the Notch protein, which is involved in cell fate specification and is localized in the sub-odontoblastic cell layer during odontogenesis, is not detected in adult dental tissues. In carious and injured teeth, nestin is expressed in a selective manner in odontoblasts surrounding the injury site, while Notch is expressed in the sub-odontoblastic layer of cells. We reproduced this physiological event in an in vitro culture system. Pulp cells cultured in the presence of (3-glycerophosphate formed mineralization nodules. As odontoblasts, pulp cells contributing to the nodule formation express type I collagen, osteonectin, dentin sialophosphoprotein, and nestin. In this in vitro assay system, nestin is up-regulated after local application of Bone Morphogenetic Protein 2 and 4. Fourier transform infrared microspectroscopy showed that both the organic and the mineral compositions of the nodules have the characteristics of human dentin and differ from those of enamel and bone. These findings show that both the molecular and the mineral characteristics of the human dentin matrix are respected in the in vitro culture conditions.

Dentigerous bones and dentition of juveniles and adults of several European Speleomantes-species were investigated using scanning electron microscopy. In the juveniles examined, all dentigerous bones bore bicuspid teeth. The adult males showed the well-known dentitional sexual dimorphism, i.e. monocuspid largely conical, elongated and strongly curved premaxillary teeth. However, teeth of the anterior portion of the maxillae and some teeth of the dentary were also clearly monocuspid; the remaining teeth had differently shaped apices considered to be different grades of bicuspidity. Vomerine teeth were exclusively bicuspid. Monocuspid, but smaller teeth were also found on the premaxilla of an adult female. The conical monocuspid tooth in adults is a modified metamorphosed tooth. Monocuspids, at least on the premaxillae, may be constantly present in males and development of monocuspids probably depends on differential sensitivities of the tooth producing tissue for androgen stimuli.

Biomimicry has been introduced as a term for innovations inspired by nature [1]. Such innovations may appear in almost every part of modern society. This review on the effects of enamel matrix proteins on the formation of cementum and the development of emdogain for regeneration of periodontal tissues lost due to periodontitis shows an example of biomimicry in dentistry. Findings from clinical and laboratory investigations are summarized and the biological basis for enamel matrix-induced periodontal regeneration is discussed.

Introduction: Revascularization is an emerging regenerative treatment protocol with little published data available in immature molar teeth. The present case series demonstrates the outcome of revascularization treatment with intracanal medicament of calcium hydroxide in immature necrotic molars. Methods: Immature necrotic permanent first molars (n = 6) of patients 8-11 years old were treated by a revascularization protocol that used 2.5% NaOCl irrigation, medication with calcium hydroxide placed in the coronal third of the root canals, induction of apical bleeding, and coronal sealing with white mineral trioxide aggregate. Among the treated teeth, 4 molars had undergone prior root canal instrumentation by the referring dentists. National Institutes of Health Image-J program with TurboReg plug-in was used for standardization of the radiographs and to determine the increase in root length and root width. Results: After a follow-up period of 10 months, all teeth demonstrated radiographic evidence of complete periapical healing, progressive thickening of dentinal walls, and continued apical development in the absence of clinical symptoms. Two uninstrumented molars showed a positive response to cold testing at 9 months. Conclusions: On the basis of a follow-up period of 10 months, the present cases demonstrate a favorable outcome of the revascularization procedure in immature necrotic molars by using calcium hydroxide medication in the coronal third of the root canals.

ML. Zeichner-David M, Fincham AG: Hertwig's epithelial root sheath differentiation and initial cementum and hone formation during long-term organ culture of mouse mandihular first molars using serumless. chemically-defined medium. J Periodont Res 1988; 23: 28-40. Studies were designed lo test the hypothesis that Hertwig's epithelial root sheath (HERS) synthesizes and secretes enamel-related proteins that participate in the process of acellular cementum formation. Our experimental strategy was to examine sequential root development of the mouse mandibular first molar in vivo and in long-term organ culture in vitro using serumless, chemically-defined medium. Using anti-amelogenin, anti-enamelin and anti-peptide antibodies, enamel-related antigens were localized within intermediate cementum during HERS differentiation and root formation in vivo. Cap stage molars maintained for periods of up to 31 days in organ culture expressed morphogenesis and cytodifferentiation as identified by tooth crown and initial root, cementum and bone formation. Metabolically-labeled HERS products were analyzed by immunodetection using enamel-related antibodies and one-and two-dimensional SDS gel electrophoresis. A 72 kDa and 26 kDa polypeptide were identified in forming mouse cementum. Both of these root putative cementum proteins yield similar (identical) amino acid compositions; however, both proteins differed from the compositions of either mouse crown enamelin or amelogeoin proteins. This approach provides a new and novel in vitro model towards understanding HERS differentiation and functions related to root and bone formation. The data support the hypothesis that HERS cells synthesize polypeptides related to but also different from canonical crown enamel proteins.

specific molecules that are distinctively expressed during murine dental differentiation Bègue-Kirn C, Krebsbach PH, Bartlett JD, Butler WT: Dentin sialoprotein, dentin phosphoprotein, enamelysin and ameloblastin: tooth-specific molecules that are distinctively expressed during murine dental differentiation. Eur J Oral Sci 1998; 106: 963-970. © Eur J Oral Sci, 1998 Dentin sialophosphoprotein [designated DSPP and cleaved into dentin sialoprotein (DSP) and dentin phosphoprotein (DPP)], enamelysin and ameloblastin are each expressed in unique fashions during tooth development. It is possible that these components participate in cell differentiation and the conversion of unmineralized matrix into mineralized structures. In order to delineate the timing and the positioning of these three molecules in a physiological context, we compared their expression profiles by performing in situ hybridization experiments on consecutive sections in developing mouse in the facing ameloblast layer, and for ameloblastin mRNA in preodontoblasts, Houston, TX 77030, USA polarizing odontoblasts and ameloblasts. Immunohistochemistry showed that Telefax: +1-713-5004568 DSP and ameloblastin transcripts were translated into proteins that were deposited at the apical pole of the differentiated cells (odontoblasts and ameloblasts, respectively). The interrelated expression profiles found for these Key words: dentin sialoprotein; dentin phosphoprotein; enamelysin; ameloblastin; tooth-specific molecules illustrate the importance of a specific molecular tooth mineralization network to initiate highly regulated processes such as cytodifferentiation and the subsequent mineralization.

To establish the normal dental development pattern of the ICR/Jcl strain of mouse, we analyzed a significant number of observations of the different developmental stages of the first mandibular molar, accurately recording the chronology of their daily embryonic development. Proliferation of the dental sheet began at day 12.5 in utero (E-12.5), the bud stage appeared at days E-13.5 and E-14.5, the cap stage was observed at days E-14.5, E-15.5 and E-16.5 and the early bell stage at day E-17.5. The presence of predentin was observed at day E-18.5 and dentin was observed 1 and 2 days after birth (D-1 and D-2). The late bell stage with presence of enamel was detected more than 3 days after birth. Embryonic and dental development in the ICR/Jcl strain of mouse is faster than in other well-known strains. The establishment of this developmental pattern will be useful for future investigations of transgenic mice. (J. Oral Sci. 46, [135][136][137][138][139][140][141] 2004)

Ectodermal dysplasia syndromes affect the development of several organs, including hair, teeth, and glands. The recent cloning of two genes responsible for these syndromes has led to the identification of a novel TNF family ligand, ectodysplasin, and TNF receptor, edar. This has indicated a developmental regulatory role for TNFs for the first time. Our in situ hybridization analysis of the expression of ectodysplasin (encoded by the Tabby gene) and edar (encoded by the downless gene) during mouse tooth morphogenesis showed that they are expressed in complementary patterns exclusively in ectodermal tissue layer. Edar was expressed reiteratively in signaling centers regulating key steps in morphogenesis. The analysis of the effects of eight signaling molecules in the TGF␤, FGF, Hh, Wnt, and EGF families in tooth explant cultures revealed that the expression of edar was induced by activin␤A, whereas Wnt6 induced ectodysplasin expression. Moreover, ectodysplasin expression was downregulated in branchial arch epithelium and in tooth germs of Lef1 mutant mice, suggesting that signaling by ectodysplasin is regulated by LEF-1-mediated Wnt signals. The analysis of the signaling centers in tooth germs of Tabby mice (ectodysplasin null mutants) indicated that in the absence of ectodysplasin the signaling centers were small. However, no downstream targets of ectodysplasin signaling were identified among several genes expressed in the signaling centers. We conclude that ectodysplasin functions as a planar signal between ectodermal compartments and regulates the function, but not the induction, of epithelial signaling centers. This TNF signaling is tightly associated with epithelial-mesenchymal interactions and with other signaling pathways regulating organogenesis. We suggest that activin signaling from mesenchyme induces the expression of the TNF receptor edar in the epithelial signaling centers, thus making them responsive to Wnt-induced ectodysplasin from the nearby ectoderm. This is the first demonstration of integration of the Wnt, activin, and TNF signaling pathways.

Following a severe traumatic incident to permanent immature teeth, the growth of calcified tissue in the pulp space may occasionally occur. This calcified tissue may be diffuse or in intimate contact with the dentine. It has been suggested that a wide Key words: dental pulp calcification/etiology; dental trauma; dentin/pathology; incisor/injuries; open apex, severe damage to the root sheath, and the absence of root canal therapy infection are only some of the predisposing factors leading to this

Carbon flow through the lysine branch of the aspartate biosynthetic pathway is a rate-limiting step in the formation of cephamycin C, a broad spectrum β-lactam antibiotic produced by Streptomyces clavuligerus. In this study, genes which encode the enzymes catalyzing the first two steps of the aspartate pathway, ask (aspartokinase) and asd (aspartate semialdehyde dehydrogenase), in S. clavuligerus NRRL 3585 were cloned and sequenced. Nucleotide sequencing and codon preference analysis revealed three complete open reading frames (ORFs). ORF2 starts within ORF1 and terminates by utilizing the same stop codon as ORF1, an arrangement typical of many ask genes. ORF3 is located 2 nucleotides downstream of ORF1,2. Database comparisons with these proteins identified ORF1 as the large (α) subunit of aspartokinase, ORF2 as the small (β) subunit of aspartokinase and ORF3 as the aspartate semialdehyde dehydrogenase. The cloned genes were functionally expressed in auxotrophic Escherichia coli strains, CGSC5074 (ask − ) and E. coli CGSC5080 (asd − ), the two enzymes were partially purified from E. coli cell extracts and their kinetic parameters were determined. The effects of end product amino acids and diaminopimelic acid on the activity of Ask and Asd enzymes were also described.  2004 Elsevier SAS. All rights reserved.