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PubMed2004

Agenesis of third molar germs depends on sagittal maxillary jaw dimensions in orthodontic patients in Japan.

The aim of this study was to determine the correlation between congenitally missing third molar tooth germs and sagittal maxillomandibular jaw dimensions in orthodontic patients in Japan. The subjects were 391 patients from the orthodontic clinic of the Hokkaido University Dental Hospital who were less than 15 years of age. Assessments were made from panoramic radiographs and lateral cephalograms. The subjects were divided into a maxillary/mandibular third molar absent and an existent group. The ANB angle and the sagittal dimensions of the nasal floor (ANS-PNS), maxillary basal bone (Mx), mandibular corpus (Go-Pog), and mandibular basal bone (Mn) were measured. Logistic regression analysis was used to estimate associations between third molar agenesis and these measures. The following results were obtained: (1) The frequency of the maxillary third molar agenesis significantly increased with decreasing Mx (odds ratio = 0.559, 95% confidence interval = 0.377 - 0.829). The frequency of the mandibular third molar agenesis also increased with decreasing Mx (odds ratio = 0.532, 95% confidence interval = 0.330 - 0.856). (2) There were no significant correlations between Mn and mandibular third molar agenesis. These results suggest that agenesis of third molar germs does not depend on anteroposterior dimensions of the mandible but depends on anteroposterior dimensions of the maxilla in Japanese orthodontic patients.

Adolescent↗
PubMed2004

The expression pattern of hyaluronan synthase during human tooth development.

In previous studies, hyaluronan (HA) and its major cell surface receptor CD44 have been suggested to play an important role during tooth development. HA synthases (HASs) are the enzymes that polymerize hyaluronan. Data on the expression pattern of HASs during tooth development is lacking and the aim of the present study was to investigate the localisation of HAS by immunohistochemistry in human tooth germs from different developmental stages. The distribution pattern of HAS in the various tissues of the "bell stage" tooth primordia corresponded to that of hyaluronan in most locations: positive HAS immunoreactivity was observed in the dental lamina cells, inner- and outer-enamel epithelium. On the stellate reticulum cells, moderate HAS signal was observed, similar to the layers of the oral epithelium, where faint HAS immunoreactivity was detected. At the early phase of dental hard tissues mineralization, strong HAS immunoreactivity was detected in the odontoblasts and their processes, as well as in the secretory ameloblasts and their apical processes and also, the pulpal mesenchymal cells. The HAS signals observed in odontoblasts and ameloblasts gradually decreased with age. Our results demonstrate that hyaluronan synthesised locally by different dental cells and these results provide additional indirect support to the suggestion that HA may contribute both to the regulation of tooth morphogenesis and dental hard tissue formation.

Ameloblasts↗
PubMed1986

An experimental study of timing and topography of early tooth development in the mouse embryo with an analysis of the role of innervation.

The putative involvement of the innervation in determining the sites of dental development was investigated by intra-ocular homografting and organ culture methods. Mandibular arches were dissected from 9 and 10-day-old (E9-E10) mouse embryos and grafted to the anterior eye chambers of homologous adult mice for 12-14 days. There was no significant difference in the incidence of tooth formation between grafts in which the trigeminal ganglion was included (n = 82, 68 per cent) or excluded (n = 72, 65 per cent). A parallel in vitro study in which E9 and E10 mouse embryo mandibular arches were cultured in the absence of trigeminal innervation showed that definitive tooth germs were formed during the 7-9 day culture period. It is concluded that innervation plays no part in determination of tooth development. In further experiments with E9 and E10 material, the complete mandibular arch, the hemimandibular arch and the ventral midline region of the mandibular arch (including the median epithelial isthmus) were each grafted for a period of 21 days. Alizarin-red whole-mount staining of recovered grafts revealed that bone had been deposited and mineralized in the majority of grafts of all types. Incisor and molar teeth with near normal crown shapes developed in grafts of complete mandibular arches. Hemimandibular arches gave rise almost exclusively to molars. Grafts of the E10 ventral midline region gave rise exclusively to incisors, but the same graft performed at E9 did not produce teeth. It is concluded that incisor primordia are localized in or near the median epithelial isthmus (and are thus destroyed or damaged when the mandibular arch is hemisected) and that incisors are not determined until E10. At E9 the odontogenic neural crest has yet to complete its ventrad migration into proximity with presumptive incisor epithelium. By this time, however, odontogenic crest and presumptive molar epithelium have already reached juxtaposition and molar primordia are fully competent. In grafts of the frontonasal and maxillary processes made at E10, prior to merging of their respective mesenchymes, frontonasal processes gave rise exclusively to incisors, whereas maxillary processes gave rise exclusively to molars.

Animals↗
PubMed2004

Opg, Rank, and Rankl in tooth development: co-ordination of odontogenesis and osteogenesis.

Osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB (RANK), and RANK ligand (RANKL) are mediators of various cellular interactions, including bone metabolism. We analyzed expression of these three genes during murine odontogenesis from epithelial thickening to cytodifferentiation stages. Opg showed expression in the thickening and bud epithelium. Expression of Opg and Rank was observed in both the internal and the external enamel epithelium as well as in the dental papilla mesenchyme. Although Rankl expression was not detected in tooth epithelium or mesenchyme, it was expressed in pre-osteogenic mesenchymal cells close to developing tooth germs. All three genes were detected in developing dentary bone at P0. The addition of exogenous OPG to explant cultures of tooth primordia produced a delay in tooth development that resulted in reduced mineralization. We propose that the spatiotemporal expression of these molecules in early tooth and bone primordia cells has a role in co-ordinating bone and tooth development.

Alveolar Process↗
PubMed1990

Temporal and spatial patterns of transforming growth factor-beta 1 expression in developing rat molars.

Regulatory peptides of the TGF-beta family affect various aspects of embryonic development. Recent immunolocalization and in situ hybridization studies have demonstrated a specific time- and tissue-dependent expression of TGF-beta 1 in the developing mouse embryo. The purpose of this study was to evaluate the distribution of TGF-beta 1 within rat molars at different stages of development, using a well-characterized antibody, highly specific for TGF-beta 1, and immunohistochemical methods of detection. TGF-beta 1 was immunolocalized intensely within the ectodermally derived stellate reticulum and the mesenchyme of the dental papilla at the bell stage of development. Marked immunostaining was also evident in the papillary layer and the reduced dental organ subjacent to ameloblasts in the differentiation and secretory phases of amelogenesis. During the formation of coronal tissues and in the pre-eruptive phase, immunoreactive TGF-beta 1 was localized conspicuously within the dental follicle overlying the tooth germ. This temporospatial pattern of expression of TGF-beta 1 appears to correlate with specific events in morphogenesis, histogenesis and cytodifferentiation during tooth development.

Ameloblasts↗
PubMedDate not supplied

Management of a fused central incisor in association with a macrodont lateral incisor: a case report.

Fusion is developmental anomaly of the dental hard tissue and is defined as the joining of 2 developing tooth germs resulting in a single large tooth structure. Different treatment methods can be used according to the requirements of the situation. The purpose of this case report was to present the multidisciplinary treatment of a patient who had a permanent maxillary left central tooth fused with a supernumerary incisor and a macrodont permanent maxillary right lateral incisor. In the radiographic evaluation, it was determined that the fused tooth had 2 separate roots. The supernumerary tooth was extracted after hemisection, and endodontic treatment was performed on the remaining portion. The distal side of the macrodont lateral incisor was recontoured, and the right central incisor was reshaped with a strip crown to provide aesthetic appearance and to gain space for the alignment of teeth. Following the restoration of the incisors, orthodontic treatment was provided.

Adolescent↗
PubMed1989

Aneurysmal bone cyst of the mandible.

A case report of aneurysmal bone cyst of the mandible in a seven-year-old boy which caused the destruction and loss of the bony crypt around the tooth germ and displacement of the unerupted tooth is presented. This unusual dental findings have not been previously reported in the dental literature.

Bone Cysts↗
PubMed2002

Actin-associated proteins in ameloblast differentiation.

Focal contacts are systems of adherens junctions of the cell-extracellular matrix type, which allow the transfer of fundamental signals from the extracellular matrix to nuclear compartments, capable of regulating adhesion, proliferation, migration and differentiation of cells. Recently, many authors have concentrated their attention on epitheliomesenchymal interactions which guide organogenesis of dental germ, identifying numerous growth and differentiation factors and having the inner enamel epithelial cells of the enamel organ as a target. Given that the two cellular compartments in their tooth germ are separated by a basal membrane and by an extracellular matrix, which touches it, we wanted to evaluate the presence of focal contacts through the identification of talin and vinculin, proteins of the actin-associated protein complex. In this study we utilized the hemimandibles of young Wistar rats and we extracted the related odontogenic tooth organs present at their apical end. Specimens are processed with antibody against vinculin and talin. Results show that these junctional system proteins are present at the apical poles of both cellular compartments suggesting that putative epithelial-mesenchymal interactions, other than marker molecules, may use focal contacts as a system for transmission of signals.

Actins↗
PubMed1984

Influence of serum on cultured murine tooth organ allotransplants.

Previous investigations indicated that in vitro culture of fetal tooth germs before allotransplantation prolonged graft survival. This study assessed the influence of different sources of serum in culture medium on post-transplant development of neonatal tooth organs. The results indicate that recipient-strain serum, but not donor-strain serum or calf serum, increased tooth survival compared with that of uncultured controls, which were rejected by the fourteenth post-transplant day. The survival curve for cultured tooth organs was shifted to the right by two days. No tooth transplant survived beyond three wk.

Animals↗
PubMed1976

The role of alveolar bone in the noneruption of molar teeth in grey lethal mice.

The in utero and neonatal development of the molar teeth in osteopetrotic grey lethal mice and normal litter mates was observed in timed embryos which were obtained by caeserian section, and in neonatal litters which were sacrificed on the day of birth and each day thereafter until day 7. Serial coronal and sagittal sections through the heads were prepared. The earliest disturbances in the alveolar bone-tooth germ complex were seen at day 19 in utero. At birth, the grey lethal first molar germs are severely distorted by encroaching alveolar bone. The abnormalities become progressively more marked until day 7. The failure in alveolar bone remodeling is the factor which prevents tooth eruption in grey lethal mice.

Alveolar Process↗
PubMed2002

Is tooth agenesis related to brainstem anomalies in myelomeningocele patients with Chiari II malformations?

Defects in the prenatal development of the brainstem can result in cranial nerve deficiencies. As the development of tooth germ is dependent on n. trigeminus, which originates from the brainstem, the hypothesis underlying this study was that anomalies of the brainstem would lead to an increased prevalence of tooth agenesis. Twenty-three patients (13 F and 10 M, age range 6-37 years) were studied, all with myclomeningocele and brainstem anomalies (Chiari II). They were examined retrospectively from the data in journals and dental radiographs and compared to available data on the prevalence of tooth agenesis in the Swedish population. Our hypothesis was rejected, since there was insignificant difference in the frequency of agenesis in our material (8.7%) compared with that of the Swedish population (7.4%).

Adolescent↗
PubMed1993

Tissue reactions towards titanium implants inserted in growing jaws. A histological study in the pig.

In this investigation, the tissue reactions towards titanium implants inserted in growing jaws of pigs were studied by means of histology. At the age of 12 weeks, 5 test pigs each received 4 Brånemark System titanium implants (fixtures). The fixtures were inserted immediately after extraction of the mesial root of the second deciduous premolar (P2) and the deciduous canine (C) on one side of the mandible and the mesial root of the first deciduous premolar (P1) on the other side. The fourth implant was placed after extraction of the deciduous lateral incisor (L) on one side in the upper jaw. Furthermore, 1 pig in which no extractions or fixture installations were performed served as a control. All pigs were followed for 165 days with clinical, radiographic and biometric examinations, the results of which have been previously presented. In this study, 10-microns-thick ground sections were produced for histology after the jaws had been fixed by immersion in formalin and further processed and embedded in plastic resin. Six of the fixtures originally inserted were lost during the experimental period, and the remaining implants were found to be involved with mineralized bone to varying degrees. Regarding the fixture-to-teeth relationship, it was found that, in the premolar region of the lower jaw, the teeth were positioned superior to and buccally angulated in relation to the fixtures. In the upper jaw, the implants were positioned below the adjacent teeth but centrally in the alveolar process. Tooth germs adjacent to the fixture had a displaced eruption path, buccally or lingually to the fixture. If the bud developed in close contact with the fixture, a changed morphology of the germ could be observed.

Alveolar Process↗
PubMed1979

Teeth transplanted across a multiple non-H-2 barrier stimulated weak cell-mediated immunity without memory.

The genetic and immunologic criteria required for successful tooth transplantation have yet to be defined. Teeth grafted across strong barriers elicit vigorous immunity. However, teeth and tooth germs transplanted to subcutaneous sites in H-2 compatible but multiple-non-H-2 disparate recipients stimulated weak in vitro cellular cytotoxicity compared with skin grafts 5 mm in diameter. Furthermore, tooth allografts did not sensitize recipients as measured by the rejection of second-set, donor skin grafts. It may be that tooth allografts provoke fewer detrimental immune mediator systems than do skin grafts across moderate to weak transplantation barriers.

Animals↗
PubMed1998

Expression and function of FGFs-4, -8, and -9 suggest functional redundancy and repetitive use as epithelial signals during tooth morphogenesis.

To elucidate the roles of fibroblast growth factors (FGF) in the regulation of tooth morphogenesis we have analyzed the expression patterns of Fgf-4, -8, and -9 in the developing mouse molar and incisor tooth germs from initiation to completion of morphogenesis by in situ hybridization analysis. The expression of these Fgfs was confined to dental epithelial cells at stages when epithelial-mesenchymal signaling regulates critical steps of tooth morphogenesis. Fgf-8 and Fgf-9 mRNAs were present in the oral epithelium of the first branchial arch at E10 and 1 day later expression became more restricted to the area of presumptive dental epithelium and persisted there until the start of epithelial budding. Fgf-8 mRNAs were not detected later in the developing tooth. Fgf-4 and Fgf-9 expression was upregulated in the primary enamel knot, which is a putative signaling center regulating tooth shape. Subsequently, Fgf-4 and Fgf-9 were expressed in the secondary enamel knots at the sites of tooth cusps. Fgf-9 expression spread from the primary enamel knot within the inner enamel epithelium where it remained until E18. In the continuously growing incisors Fgf-9 expression persisted in the epithelium of the cervical loops. The effects of FGFs were analyzed on the expression of the homeobox-containing transcription factors Msx-1 and Msx-2, which are associated with tissue interactions and regulated by the dental epithelium. Locally applied FGF-4, -8, and -9 stimulated intensely the expression of Msx-1 but not Msx-2 in the isolated dental mesenchyme. We suggest that the three FGFs act as epithelial signals mediating inductive interactions between dental epithelium and mesenchyme during several successive stages of tooth formation. This data suggest roles for FGF-8 and FGF-9 during initiation of tooth development, and for FGF-4 and FGF-9 during regulation of tooth shape. FGF-9 may also be involved in differentiation of odontoblasts. The coexpression of Fgfs with other signaling molecules including Shh and several Bmps and their partly similar effects suggest that the FGFs participate in the signaling networks during odontogenesis.

Animals↗
PubMed1998

Relationship between growth and the pattern of tooth initiation in alligator embryos.

The temporal and spatial patterns in which teeth are initiated in the growing jaws of embryos are constant for a species but different for different species. The sources of the patterns have been explained in two ways. First, they are the outcome of reactions between molecules created at stationary targets and those which diffuse through embryonic tissues (e.g., Edmund, 1960). Second, Osborn (1978) supposed that the patterns mirror the way a (mixed) population of parent cells, the tooth clone, grows. Westergaard and Ferguson (1986, 1987, 1990) concluded, from their observations of the sequence of tooth initiation in alligators, that the complicated sequences in which 20 teeth are initiated in each tooth quadrant could not be explained by jaw growth. The present study attempts to refute this criticism by means of measurements made from the raw data published by Westergaard and Ferguson. These data reveal that new teeth, here called primary teeth, are added at a constant rate at the back of the jaw. Interstitial growth of the cells between primary teeth creates space for secondary teeth in secondary regions. The secondary regions increase in length exponentially with time. The sequence in which teeth are initiated in the growing secondary regions was found to be the same in every part of the upper and lower jaws. It was accurately reproduced by a computer program based on a linear contraction rate of inhibitory zones and exponential growth of secondary regions. The results suggest that the posterior progress zone in alligator embryos grows about 125 microm a day. Newly initiated tooth germs are surrounded by an inhibitory zone about 250 microm in diameter. These zones contract from 20 to 30 microm a day until they are about 170 microm in diameter. The sequences in which tooth positions are initiated in embryos may be more the result of the pattern in which cells escape from molecules that inhibit induction rather than the pattern in which cells create molecules that initiate induction.

Alligators and Crocodiles↗
PubMed1995

Midkine (MK), a heparin-binding growth/differentiation factor, is regulated by retinoic acid and epithelial-mesenchymal interactions in the developing mouse tooth, and affects cell proliferation and morphogenesis.

Midkine (MK) is the first cloned gene in a new family of heparin-binding growth/differentiation factors involved in the regulation of growth and differentiation. We have analyzed the expression of MK mRNA and protein during tooth development in mouse embryos and studied the regulation of MK expression and the biological effects of MK protein in organ cultures. MK expression was restricted and preferential in the tooth area as compared to the rest of the developing maxillary and mandibular processes suggesting specific functions for MK during tooth morphogenesis. MK mRNA and protein were expressed during all stages of tooth formation (initiation, morphogenesis, and cell differentiation), and shifts of expression were observed between the epithelial and mesenchymal tissue components. However, the expression of mRNA and protein showed marked differences at some stages suggesting paracrine functions for MK. Tissue recombination experiments showed that MK gene and protein expression are regulated by epithelial-mesenchymal interactions, and, moreover, that dental tissue induces the ectopic expression of MK protein in non-dental tissue. The expression of MK gene and protein in the mandibular arch mesenchyme from the tooth region were stimulated by local application of retinoic acid in beads. Cell proliferation was inhibited in dental mesenchyme around the beads releasing MK, but this effect was modulated by simultaneous application of FGF-2. Morphogenesis and cell differentiation were inhibited in tooth germs cultured in the presence of neutralizing antibodies for MK, whereas the development of other organs (e.g., salivary gland, kidney) was unaffected. These results suggest important roles for MK in the molecular cascade that regulates tooth development.

Animals↗
PubMed1989

The fine structure of initial mineralisation during tooth development in the gummy shark, Mustelus manazo, Elasmobranchia.

In the enameloid matrix a large number of tubular vesicles appeared around the odontoblast processes at the stage of enameloid matrix formation. The tubular vesicles were limited by unit membrane and the membrane often seemed to connect with that of the odontoblast processes. The tubular vesicles probably originated from the odontoblasts. Electron-dense granules were observed in the tubular vesicles before the appearance of crystals and then, in the stage of mineralisation, initial enameloid crystals appeared in each tubular vesicle. Parts of the odontoblast process surrounded small aggregations of tubular vesicles in the unmineralised dentine matrix. There were many multivesicular bodies and lysosomes in the odontoblasts forming the dentine. The odontoblasts probably absorb and break down the tubular vesicles after the beginning of dentinogenesis. Only in the predentine, during the enameloid maturation stage, did a few matrix vesicles appear, but no crystals were found in them. Hence, the initial mineralisation in tooth germs of the shark can be said to be different from that in teleosts.

Amelogenesis↗
PubMed1994

Stage-specific expression of decapentaplegic-Vg-related genes 2, 4, and 6 (bone morphogenetic proteins 2, 4, and 6) during human tooth morphogenesis.

Members of the decapentaplegic-Vg-related (DVR) gene family are diffusible signaling molecules regulating inductive tissue interactions during vertebrate development. Expression of DVR/bone morphogenetic protein (BMP) 2, 4, and 6 was studied in human fetal teeth. Sequential morphogenetic stage-specific studies of DVR/BMP 2 and 4 mRNA expression by in situ hybridization revealed transcripts for DVR/BMP 4 during compaction of the dental mesenchyme. In contrast, DVR/BMP 2 mRNA appeared later during tooth development and was located in differentiated cells (odontoblasts). These results were confirmed by reverse-transcription polymerase chain reaction (RT-PCR), which detected DVR/BMP 2 and 4 mRNA in human tooth-germ samples. DVR/BMP 6 protein was distributed in the early dental epithelium and, later, in pre-odontoblasts and odontoblasts, where it remained during dentin formation. These results suggest that DVR/BMP 4 is involved in the early tooth morphogenesis. DVR/BMP 6 may, in particular, be implicated in epithelial-mesenchymal interactions controlling cytodifferentiation. DVR/BMP 2 and 6 may also be involved in odontoblast secretory function. The results suggest that members of the DVR gene family may play regulatory roles during human tooth development.

Base Sequence↗