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PubMed1984

The sensitivity of the developing tooth germ to systemic disturbances.

Deciduous tooth germs were removed from 76 babies who were either stillborn or had died in infancy. Lines in enamel or dentine were identified histologically. A chronological association was found between these lines and systemic illness in the child or pregnant mother in half the cases studied. Enamel was more sensitive to environmental factors than dentine, but causes of disturbance appeared to be non-specific. Teeth are a sensitive but non-specific index of environmental disturbance.

Dental Enamel↗
PubMed2003

[The expression and function of Smad7 during human tooth germ development].

OBJECTIVE: To observe the temporal and spatial expression of Smad7 during human tooth germ development and evaluate the effect of Smad7 on tooth germ development. METHODS: The expression of Smad7 and its changes at different stages of human tooth germ were detected by using immunohistochemical staining. RESULTS: Smad7 was expressed at all stages of tooth germ, but the distribution patterns at various stages were different. It indicated that temporal and spatial expressing mode of Smad7 during human tooth germ development was specific, which was similar to that of TGF-beta its signal transducer Smad2/3. CONCLUSION: Smad7 might play an important role in TGF-beta intracellular signaling for modulating the differentiation of ameloblasts and odontoblasts.

Ameloblasts↗
PubMed1985

Orally administered methionine alters the growth of tooth germs in newborn rats.

The effects of methionine intubation via gastric needle on the growth of incisor and molar tooth germs in newborn rats were investigated. Upon delivery, the pups were divided into groups of 8 and randomly assigned to dams which were then randomly assigned to three groups. Then the pups were intubated in the stomach with (a) no methionine - group I, (b) 0.1 g methionine per 100 g body weight - group II, or (c) 0.2 g methionine - group III, from day 3 to day 13 on every other day. At day 15, the average body weights of pups among the three groups showed no difference statistically, though animals in group III showed a 17.5% mortality rate; there were no deaths in the other two groups. There was inadequate hair growth in some pups in group III. The weights of incisor and of molar tooth germs in group II were heavier than in groups I and III. The total hydroxyproline content of incisor tooth germs in group II was also greater than in the other groups, whereas there was no difference in molar tooth germs on this parameter among all groups. Collagen synthesis of both tooth germs was highest in group III compared to other groups. The total amount of calcium in both tooth germs showed no difference among groups, but values were consistently higher in group II. 45Ca uptake showed no difference among groups. The present results indicate that the amount of methionine received by growing pups alters the composition of developing tooth germs, but that incisor and molar tooth germs are affected differently.

Administration, Oral↗
PubMed1999

The effect of mechanical trauma on the tooth germ of rat molars at various developmental stages: a histopathological study.

Intrusive trauma was experimentally applied to the tooth germ at different developmental stages in the rat first molar. The tooth germ at the earliest (postnatal day 1, initiating stage of enamel matrix formation) and the latest (postnatal day 10, calcifying stage of preformed enamel matrix) developmental stages studied showed localized enamel hypoplasia as a direct sequela of trauma. The tooth germs in which enamel matrix was rapidly thickening (postnatal days 3, 5, 7) and had not yet started to calcify showed the most intense and extensive injuries to the formation and structural organization of both enamel and dentin. As for indirect effects secondary to trauma, tooth germ dislocation was observed chiefly in tooth germs at the same developmental stages, frequently resulting in ankylosis. The present experimental model may be helpful for clarifying the histogenesis of traumatic changes in the developing tooth germ.

Ameloblasts↗
PubMed2004

Accelerated bone formation and increased osteoblast number contribute to the abnormal tooth germ development in parathyroid hormone-related protein knockout mice.

Our previous study showed that tooth germs at late embryonic stage [later than embryonic day 17.5 (E17.5)] and neonatal homozygous parathyroid hormone-related protein (PTHrP)-knockout mice are compressed or penetrated by the surrounding alveolar bone tissue. In vivo and in vitro studies have shown that the development of the tooth germ proper is not disturbed, but insufficient alveolar bone resorption, due to the decreased number and hypofunction of osteoclasts, is the main cause of this abnormality. In addition to the insufficient alveolar bone resorption, progressive bone formation toward tooth germs was observed in homozygous mice, suggesting that accelerated bone formation also contributes to this abnormality. To further investigate this, homozygous mice at E14.0 and E15.5, when alveolar bone is forming, were used for histochemical and bone histomorphometric analyses. In contrast to the late embryonic stage, the alveolar bone did not yet compress developing tooth germs in homozygous mice on E14.0, but a larger amount of bone tissue was seen compared to wild-type littermates. Histomorphometric analysis of bone at E14.0 revealed that the osteoblast numbers and surfaces in the mandibles and in the bone collar of femora of homozygous mice were significantly higher than those of wild-type mice. However, unlike our previous study showing the osteoclast surface on E18.5 in homozygous mice to be significantly lower than that of wild-type mice, this study at E14.0 showed no significant difference between the two genotypes. To evaluate the amount of calcification around tooth germs, 3D images of mandibles were reconstructed from the calcein-labeled sections of the wild-type and mutant mice. Labeling was performed at E14.0, and the mice were sacrificed 1 h after the calcein injection to minimize the effect of bone resorption. Comparison of the 3D images revealed that the labeled surface was larger around developing tooth germs in homozygous mouse than in wild-type mouse. On day E15.5, osteoblasts approached the enamel organ of homozygous mice but this was not observed in wild-type mice. In this study, we report a systemic increase in osteoblast number and accelerated bone formation in homozygous PTHrP-knockout mice, both of which contribute to the abnormal tooth development.

Acid Phosphatase↗
PubMed2001

Apoptosis in regressive deciduous tooth germs of Suncus murinus evaluated by the the TUNEL method and electron microscopy.

Apoptosis in regressive primary (deciduous) dental primordia was examined in the embryos of Suncus murinus, which is a monophyodont. The primary tooth germs of S. murinus are temporarily formed and disappear during the embryonic period before they are calcified. Most primary tooth germs reach the bell stage and degenerate by embryonic day 22 (E22). Light microscopy on haematoxylin-eosin-stained sections revealed that intensely labelled granular substances are frequently present in the epithelial portion (enamel organs) of the deciduous tooth germs during the period from E18 to E20. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labelling method, computer-assisted three-dimensional reconstructions, and electron microscopy confirmed that these variable-sized granular substances are similar to apoptotic cells or bodies. Apoptotic structures were mainly found in the primary tooth germ located on the buccal surface of the secondary (successional) tooth germ. These results lead to the conclusion that apoptosis is closely associated with the involution and disappearance of the deciduous tooth germ in S. murinus. A primary tooth germ was observed on the buccal side of all the corresponding successional tooth germs, although the buccal surface of the secondary tooth germ of third upper molar teeth developed only to epithelial thickening without mesenchymal condensation. The findings, therefore, suggest that apoptosis is responsible for disappearance of the primary dental primordia during tooth development in S. murinus.

Animals↗
PubMed1996

Long-term histopathologic findings in tooth germs autotransplantation. Analysis of a series.

Tooth germ autotransplantation, a surgical technique based upon extraction of a germ followed by reimplantation in the same individual, is indicated in tooth agenesis or loss as an alternative to traditional methods of treatment. The success of autotransplantation relies on several factors, and clinical studies indicate that results are excellent if correct surgery is carried out. This work offers a morphological contribution to the understanding of post-transplantation changes of the pulp, periodontal ligament and root cementum.

Dental Cementum↗
PubMed2006

Cell proliferation in teeth reconstructed from dispersed cells of embryonic tooth germs in a three-dimensional scaffold.

Tissue engineering can now reproduce tooth from postnatal tooth cells. However, crown formation is not accurately reconstituted, even when the complex structure of the enamel dentin is reproduced. Here, we showed that a tissue-engineered (TE) tooth, exhibiting morphogenesis according to regular crown-cusp pattern formation, was produced by embryonic tooth germ cells in a three-dimensional scaffold. Heterogeneous cells dissociated from embryonic day 14 (E14) mice tooth germs were seeded on a scaffold and implanted under a kidney capsule in adult mice. The developmental process of the implants was examined for up to 14 d. At 5 d, the cells had formed initial tooth germ, followed by enamel-covered dentin tissue formed symmetrically. To study the developmental process, we examined the growth pattern using 5-bromo-2'-deoxyuridine (BrdU)-labeling analysis. The initial cell-proliferation patterns of the TE teeth were similar to that at the cap and early bell stages in natural teeth. This was particularly true in the cervical loop, which showed a similar distribution pattern of BrdU-positive cells in TE- and natural teeth. These results suggested that even when embryonic tooth germs are dissociated, the single cells can reconstitute tooth, and that enamel organ morphogenesis proceeds as in natural teeth.

Animals↗
PubMed1982

Development of rotation of mandibular premolar tooth germs in the dog.

The development of premolar tooth germs in dogs, particularly their rotation and crowding, was examined on radiographs, dissected specimens of tooth germs, serial sections stained by Masson-Goldner's technique and reconstructed models. The materials used were the mandibles of 32 puppies from birth to 6 months, and the species was a highly pedigreed Shiba Inu which has no crowding of the premolars in the mature stage. The results obtained are as follows. (1) Rotations and crowdings of premolars, similar to those in brachygnathus dogs and wolves raised in captivity, were observed during ontogenesis of dolichocephalic dogs, whose adult state exhibits no crowding of teeth. (2) The type of rotation was B (the mesial portion is rotated buccally) for the second and third premolars and L (the mesial portion lingually) for the fourth premolar. (3) The rotations of the premolars did not coincide with those of their deciduous predecessors. (4) These rotations appeared in the bud and cap stages of premolars, before the formation of roots of deciduous molars. The premolars developed crowding at 5 months when they increased in dimension.

Aging↗
PubMed1979

Sensitivy of mouse molar tooth germs to x-ray irradiation in vitro.

Molar tooth germs, extirpated from 18-day mouse fetuses were cultured on Millipore filter strips in Falcon organ culture dishes. The tooth germs were exposed to 250 kVcp X-rays at 106 R/min. for a total exposure of 1 600 R. Tissues were harvested on a daily basis for a total period of 12 days and were examined microscopically, utilizing H and E stain. Severe disorganization of the tooth germs was evident within 24 hours of irradiation. The basement membrane became hyalinized; pyknotic nuclei and lysed cells were observed throughout the dental papilla, but mostly in the regions of the presumptive cusps. Although a thin layer of predentin was elaborated by the odontoblasts, the matrix failed to calcify and enamel matrix was not produced. Cultures older than 10 days demonstrated extensive cell death. The entire pulp was reduced to a mass of necrotic cells and the ameloblastic layer consisted of an epithelial remnant covering the cuspal tips.

Ameloblasts↗
PubMed1978

Action of 5-bromodeoxyuridine on tooth germs "in vitro". II. - Effects on collagen synthesis.

The first lower molar tooth germs removed from 16-day-old mouse embryos were cultured for 2 days on a standard medium and then for 24 hours on the same medium containing BrdU (treated tooth germs) or not (controls). We attempted to study the effects of 5-Bromodeoxyuridine on the type I and type III collagen synthesis 24 (stage 16 + 4) and 72 (stage 16 + 6) hours after the incorporation of this thymidine analogue. At stage 16 + 4, type I and type III collagen were synthesized both in control and BrdU-treated tooth germs. However BrdU induced quantitative modifications in the type I collagen synthesis which might be explained by modifications in the turnover of this type of collagen. At stage 16 + 6, the BrdU treatment resulted in the inhibition of the terminal differentiation of odontoblasts. Consequently, the normal amplification of collagen type I synthesis could not occur. However, both control and BrdU-treated tooth germs synthesized type I and type III collagen. Quantitatively, the synthesis of type III collagen was slightly affected by BrdU treatment.

Animals↗
PubMed2005

Type II/III Runx2/Cbfa1 is required for tooth germ development.

Runx2/Cbfa1 is an essential transcription factor for osteoblast differentiation and bone formation. Runx2/Cbfa1 knockout mice showed both a complete lack of ossification and the developmental arrest of tooth germ. We here report Runx2/Cbfa1 isoform-type specific functional roles in the development of tooth germ by the administration of antisense phosphorothioate oligodioxynucleotides (S-ODNs) into cultured mouse mandibles. The administration of type II/III Runx2/Cbfa1 antisense S-ODNs into the culture media resulted in an arrest of tooth germ growth at the bud-like stage in cultured mandible taken from the 11-day-old embryos, while also causing the inhibition of the differentiation of odontogenic cells into ameloblast and odontoblast in cultured tooth germs taken from the 15-day-old embryos. The expression of dentin matrix protein 1, dentin sialophosphoprotein, amelogenin, and ameloblastin was shown to be markedly suppressed in cultured tooth germ by the semi-quantitative RT-PCR. Meanwhile, no developmental arrest of tooth germ, no inhibition of gene expression, or differentiation of odontogenic cells was observed in samples treated with the type I Runx2/Cbfa1 antisense S-ODNs. The same findings were also observed in either the control or the sense and random sequence S-ODNs-treated samples. These data indicate that the type II/III Runx2/Cbfa1 isoform is closely related to the development and differentiation of tooth germ.

Animals↗
PubMed1998

Regulation by serotonin of tooth-germ morphogenesis and gene expression in mouse mandibular explant cultures.

Serotonin (5-HT) stimulates tooth-germ development in embryonic mouse mandibular explant cultures, but it is not clear whether this is due to a direct action on epithelial-mesenchymal interactions, or whether development was stimulated indirectly by serotonergic regulation of other morphoregulatory molecules. A calcium-binding protein, S-100beta, and the extracellular-matrix molecule, tenascin, two molecules thought to be important in craniofacial development, together with cartilage proteoglycan core protein, a marker for chondrogenesis, are modulated by serotonergic ligands in mandibular micromass cultures. Here, it was demonstrated that 5-HT stimulates expression of cartilage proteoglycan core protein, and inhibits expression of S-100beta and tenascin in mandibular explants. Further, ondansetron (Zofran), a 5-HT3 receptor antagonist, and NAN-190, a 5-HT1A antagonist, reversed the serotonergic stimulation of core protein and tooth germ development. In contrast serotonergic modulation of S-100beta and tenascin expression was not reversed by any of the 5-HT receptor antagonists tested, although the 5-HT uptake inhibitor, fluoxetine, did reverse the effect of 5-HT on S-100beta expression, as well as tooth-germ development. These results support previous work suggesting that 5-HT plays an important part in craniofacial development, especially in dentinogenesis and chondrogenesis. However, the possibility that tenascin or S-100beta mediate the effects of 5-HT on tooth-germ development is not supported. Rather, these results raise the possibility that 5-HT may exert effects directly on tooth-germ morphogenesis mediated by intracellular uptake of 5-HT and/or activation of 5-HT1A and 5-HT3 receptors.

Aggrecans↗
PubMedDate not supplied

45Ca uptake in tooth germs: effects of parathormone, calcitonin and propranolol.

Tooth germs harvested from 6-day-old rats were incubated in a 45Ca-containing medium for 6 hours. The addition of PTH consistently stimulated the increase in 45Ca uptake, while calcitonin significantly reduced both the PTH-stimulated incorporation and the spontaneous one. Dibutyrul CAMP (3.5 mM) had no effects. Propranolol significantly inhibited the spontaneous and stimulated 45Ca uptake. Results obtained support the concept that the two hormones have a clear influence on calcium entering the tooth germs in full calcification process probably by early membrane effect.

Animals↗
PubMed2004

Osteoclastogenesis during mouse tooth germ development is mediated by receptor activator of NFKappa-B ligand (RANKL).

To accommodate developing tooth germ in the alveolar bone, active bone resorption and the recruitment of numerous osteoclasts are essential. Recently, the signaling of receptor activator of nuclear factor-KappaB (RANK) and its ligand (RANKL) was reported to play a pivotal role in osteoclast formation and activation. The aim of this study was to examine the expression of RANKL and the contribution of RANK-RANKL signaling to the process of tooth germ and alveolar bone development. In situ hybridization showed RANKL was expressed in dental follicle cells and osteoblasts on the alveolar bone surface surrounding developing tooth germs. To elucidate the function of RANKL, mouse mandibular explants on embryonic day 14 were subjected to organ culture with osteoprotegerin (OPG), an inhibitor of RANK-RANKL signaling as a decoy receptor of RANKL. Many tooth germs were compressed with the surrounding bone tissue in the OPG-treated explants, whereas these abnormalities were not seen in untreated explants. The numbers of tartrate-resistant acid phosphatase (TRAP)-positive osteoclastic cells aligning on the alveolar bone surface were significantly decreased in OPG-treated explants compared with untreated explants. Moreover, TRAP-positive osteoclastic cells were not observed along the alveolar bone surfaces depressing tooth germs. These observations suggest that osteoclastogenesis in the alveolar bone, which is essential for the accommodation of normal tooth development, is mediated by RANK-RANKL signaling.

Acid Phosphatase↗
PubMed1995

Sonographic depiction of fetal tooth germs.

Recently, sonography of the fetal face has gained increasing importance in prenatal diagnosis. It is not yet clear whether sonographic depiction of fetal tooth germs would have an influence on the prenatal diagnosis of ectodermal dysplasia syndromes. During routine malformation screening, horizontal sections of fetal jaws were visualized and examined for tooth germs in 124 pregnant women following sonographic 'facing'. Histological jaw sections of fetuses that had died in utero at various gestational ages were produced in order to examine the degree of correspondence between the sonographic and histological findings. At least four tooth germs were found in the jaws of all fetuses between 19 and 34 gestational weeks (n = 104). Although jaw visualization was possible between 14 and 18 gestational weeks (n = 20), the exact number and location of the tooth germs could not be determined. Assessment of tooth germs may become increasingly important, as aplasia of the tooth germs is one of the principal signs of various hereditary ectodermal diseases.

Anodontia↗
PubMed1998

[The effect of retinoic acid on crown morphogenesis of mouse tooth germs in vitro].

OBJECTIVE: To study the effects of retinoic acid on crown morphogenesis of early tooth germs. METHODS: Mouse tooth organ culture model was used and the functions of different retinoic acid concentration on the first mandibular molar germs of 14-day old mouse embryo were examined. RESULTS: The first mandibular molar germ of 14-day old mouse was at the bud stage. After 6 days culture, tooth germs in culture medium (not containing retinoic acid) developed from bud stage to bell stage and formed normal cusps. The morphogenesis of tooth germs in medium containing 1 x 10(-7) mol/L retinoic acid was similar to molar germs in the medium without retinoic acid. When the concentration of retinoic acid increased to 1 x 10(-6) mol/L, the mouse tooth germs still developed from bud stage to bell stage, but normal cusps was not formed. CONCLUSION: The results suggest that high concentration of retinoic acid alter crown morphogenesis of tooth germs.

Animals↗