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PubMed2003

The regulation of bone resorption in tooth formation and eruption processes in mouse alveolar crest devoid of cathepsin k.

Osteoclastic bone resorption has recently been implicated in the tooth formation and eruption in alveolar bone. Cathepsin K (CK) is a cysteine proteinase expressed predominantly in osteoclasts and is believed to play a critical role in degradation of bone matrix proteins. Here we present evidence that the alveolar bone resorption is essential for the tooth formation and that eruption proceeds normally in CK-deficient (CK-/-) mice. Radiographic and histological analyses revealed that the alveolar bone from these animals had no significant abnormalities during the tooth development between 5 and 28 days after birth. The tooth crown was normally erupted through the alveolar bone layer at 28 days after birth. The number of tartrate-resistant acid phosphatase-positive multinuclear cells in the alveolar bone around the tooth germ was apparently increased in 5-day-old CK-/- mice compared with age-matched littermates. More important, however, the immunohistochemical localization of matrix metalloproteinase-9 (MMP-9) was clearly increased in the CK-/- osteoclasts. In contrast, no significant difference in the immunoreactivity for cathepsin D was observed between the CK-/- osteoclasts and the wild-type ones. These results indicate that CK-/- osteoclasts are fully differentiated and are capable of degrading the organic phase of alveolar bone during the tooth formation and eruption, which may result from the compensatory action by MMP-9 increasingly expressed in the osteoclasts.

Alveolar Bone Loss↗

PubMed1993

EGF receptor and its ligands, EGF and TGF-alpha, in developing and neoplastic human odontogenic tissues.

Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) regulate cell proliferation and functional maturation through the EGF receptor (EGF-R). Their roles in human tooth development and odontogenic tumorigenesis have not been explored. We studied the expression of EGF, TGF-alpha and EGF-R in human fetal teeth (cap stage to early hard tissue formation) and various odontogenic tumors. EGF-R mRNA and immunoreactive cells were mostly located in odontogenic epithelium. EGF-R expression was subject to temporospatial variation at different stages of tooth development. EGF and TGF-alpha mRNAs were detected in fetal teeth only by the reverse transcription polymerase chain reaction (RT-PCR). However, EGF and TGF-alpha immunoreactive cells were demonstrated in epithelial elements of tooth germ, suggesting that the peptides partially originate from non-odontogenic sources. In odontogenic tumors, EGF-R mRNA and immunoreactivity were confined to neoplastic epithelium. Transcripts for TGF-alpha but not for EGF were detected in tumors of odontogenic epithelial, epithelial-ectomesenchymal and ectomesenchymal origins. It is concluded that regulation of EGF-R expression is developmentally regulated in human odontogenesis. Furthermore, the odontogenic epithelium is the main target tissue for both EGF and TGF-alpha during tooth development. TGF-alpha and its receptor may also be involved in odontogenic tumorigenesis.

Adolescent↗

PubMed1999

Expression of DLX5 during human embryonic craniofacial development.

Dlx (distal-less gene) homeogenes encode transcription factors that are involved in the patterning of orofacial skeleton derived from cephalic neural crest cells. In order to study the role of DLX genes during embryonic development in human, DLX5 expression pattern was investigated in 6- to 11-week-old human embryos. A DLX5 PCR fragment was amplified from a human dental cDNA library subcloned and used for in situ hybridization investigations. DLX5 gene expression was primarily detected in the mandible at 6 weeks and then, after in the maxilla. DLX5 gene expression became restricted to progenitor cells of developing tooth germs, bones and cartilages of mandible and maxilla. During odontogenesis from bud to late cap stages, DLX5 transcripts were present in both dental epithelium and mesenchyme tissues. DLX5 expression was restricted to few cells in the vestibular aspect of the dental epithelium, while DLX5 mRNA signal was more widely distributed in dental mesenchyme. The observed expression pattern of DLX5 homeogene extends the proposed site-specific combination of homeogene expression in neural crest derived cells to human specific dentition. Furthermore, during the bud and cap stages of tooth morphogenesis, the asymmetric expression of DLX5 in the dental epithelium and dental mesenchyme may contribute to the complex patterning of human tooth shape.

Brain↗

PubMed2003

Development of a novel mouse osteoclast culture system including cells of mandibular body and erupting teeth.

Osteoclasts are multinucleated cells with the specialized function of resorbing calcified tissues. These cells develop from hemopoietic cells of the monocyte-macrophage lineage with the support of osteoblasts/stromal cells. Tooth eruption is a vertical movement of teeth via creation of an eruption pathway in and through the alveolar bone. The precise cellular and molecular determinants of tooth eruption are not yet clear, and a cell culture system that can reproduce the activity of osteoclast formation during tooth eruption is expected to be a useful tool to clarify the mechanism of eruption pathway formation. To this end, mandibular bodies, including incisors and molars, were isolated from 9- to 11-day-old mice undergoing active tooth eruption. Primary cells were obtained from mandibular bodies by enzymatic digestion and cultured in alphaMEM containing 15% FBS without any cytokine or growth factor or hormone in the culture (AFT culture, for alveolar bone, dental follicle, and tooth). A progressive increase in the number of tartrate-resistant acid phosphatase-positive multinucleated osteoclastic cells was observed in AFT culture. The osteoclastic cells generated were immunopositive for cathepsin K and calcitonin receptor, and formed resorption pits when cultured on dentine slices. Parathyroid hormone-related protein (PTHrP), expressed by the enamel organ of tooth, is reported to be an essential factor in creation of the eruption pathway. To verify this point, cells were isolated from mandibular bodies from which all teeth and dental follicles had been removed and cultured similarly (A culture, for alveolar bone). Osteoclastic cells were not formed and PTHrP production was hardly detected in the medium of A culture, in contrast to the high level of PTHrP in AFT culture. Since our previous study demonstrated that neonatal homozygous PTHrP-knockout mice show impaired osteoclastogenesis around tooth germs, AFT culture was performed by using this sample to examine whether this culture system can reproduce the status of osteoclastogenesis observed in vivo. The result showed that none of the osteoclastic cells were generated from cells of homozygous mice. We here report a novel mouse osteoclast culture system that reproduces the activity of osteoclast formation around erupting teeth without addition of any cytokine or growth factor or hormone to the medium. Histological examination of various transgenic and mutant mice now offers valuable findings on studies of tooth eruption and the present culture system using these animals would be a powerful tool in clarifying the cellular and molecular mechanisms of eruption pathway formation.

Animals↗

PubMed2006

[Odontogenic myxoma of the maxillary].

INTRODUCTION: Odontogenic myxoma is a rare benign tumor that arises from the mesenchymal portion of the tooth germ. It has a va-riable non-specific clinical and radiological appearance, and may be confused with other lesions such as ameloblastoma. CASE REPORT: We describe the case of a young, African male patient with a large odontogenic myxoma of the maxillary. The patient presented a painless firm swelling of the left maxillary. The radiograph showed a radiolucent lesion that was compatible with several diagnoses. DISCUSSION: The diagnosis was based on clinical, radiographic and histopathologic features. This tumor is locally aggressive, inducing important facial deformation and tooth displacement. Radical treatment with surgery or prosthesis is needed due to the high rate of recurrence.

Adult↗

PubMed1992

Immunolocalization of acidic and basic fibroblast growth factors during mouse odontogenesis.

Acidic and basic fibroblast growth factors (aFGF and bFGF), are both known to bind to extracellular matrix components, particularly proteoheparin sulfates, and to regulate in vitro proliferation, differentiation and morphology of cells of neuroectodermal and mesodermal origins. Their patterns of distribution were studied during mouse odontogenesis by means of indirect immunofluorescence and immunoperoxidase histochemistry on frozen fixed sections and after Bouin's fixative and paraffin embedding. Localization of aFGF on frozen fixed sections was observed in the oral epithelium, dental lamina and oral mesenchyme (day-12 of gestation), the stellate reticulum and oral epithelium (day-14), the stratum intermedium and at the basal and apical poles of preameloblasts at bell stage. After birth aFGF epitopes were localized within the predentin-dentin area, the stratum intermedium and at the secretory pole of ameloblasts. There was no staining with anti-aFGF antibodies after Bouin's fixative and paraffin embedding. In contrast, using this protocol, intense stainings were found with anti-bFGF antibodies predominantly within dental and peridental basement membranes and mesenchyme: staining of the dental basement membranes was transient (bud and cap stage) and discontinuous; a preferential concentration of bFGF epitopes in the condensed dental mesenchyme of incisors (cap stage) and the dental papillae mesenchymal cells of molars (bell stage) was observed in the posterior and the cervical part of tooth germs. An intense immunostaining of the stellate reticulum with anti-bFGF antibodies was also found on paraffin sections from bud to bell stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1998

Delta-notch signaling in odontogenesis: correlation with cytodifferentiation and evidence for feedback regulation.

Recent data suggest that dental cells utilize the evolutonarily conserved Notch-mediated intercellular signaling pathway to regulate their fates. Here we report on the expression and regulation of Delta1, a transmembrane ligand of the Notch receptors, during mouse odontogenesis. Delta1 is weakly expressed in dental epithelium during tooth initiation and morphogenesis, but during cytodifferentiation, expression is upregulated in the epithelium-derived ameloblasts and the mesenchyme-derived odontoblasts. The expression pattern of Delta1 in ameloblasts and odontoblasts is complementary to Notch1, Notch2, and Notch3 expression in adjacent epithelial and mesenchymal cells. Notch1 and Notch2 are upregulated in explants of dental mesenchyme adjacent to implanted cells expressing Delta1, suggesting that feedback regulation by Delta-Notch signaling ensures the spatial segregation of Notch receptors and ligands. TGFbeta1 and BMPs induce Delta1 expression in dental mesenchyme explants at the stage at which Delta1 is upregulated in vivo, but not at earlier stages. In contrast to the Notch family receptors and their ligand Jagged1, expression of Delta1 in the tooth germ is not affected by epithelial-mesenchymal interactions, showing that the Notch receptors and their two ligands Jagged1 and Delta1 are subject to different regulations.

Animals↗

PubMed1979

Oral aspects of osteopetrosis.

The characteristic feature of osteopetrosis is a lack of osteoclastic activity, leading to a series of somatic problems for afflicted persons. The life span of osteopetrotic patients has increased in recent years, thereby making oral aspects of the disease more evident. Four children with malignant osteopetrosis, born between 1967 and 1975, were examined. In all patients the anterior teeth were of normal shape, and erupted on schedule. Primary molars and all permanent teeth were greatly distorted, and remained totally or partly embedded in basal bone. Vertical growth of alveolar ridge was very limited. Where a fenestration of overlaying mucosa had occurred, a localized progressive osteitis developed, leading to soft tissue inflammation and, in two cases, extraoral mandibular fistulas. Peridontal attachment was very poor, spontaneous exfoliation had occurred in all patients. In two children tooth germs and necrotic bone were surgically removed. No beneficial effect of the treatment was observed. Large doses of antibiotics were needed to control recurring infections. No means of curing progressive osseous destruction of mandibular bone has been found. The general prognosis is poor.

Child↗

PubMed1990

[Clinical study of ectopic eruption of the permanent first molars].

The purpose of this study was to investigate the etiology and characteristics of the ectopic eruption of first permanent molars. The subjects were 35 cases (27 maxilla and 8 mandible) with ectopically erupted permanent first molars, which were recognized in 24 out-patients (10 boys and 14 girls) visiting Tohoku University, Dental Hospital. The materials used for the analysis were dental casts, X-ray lateral cephalograms and panoramic radiographs, and both materials of the ectopic and normal groups were compared. The results were as follows: 1) There were no significant differences statistically between the mesio-distal crown diameters of the maxillary permanent first molar, central and lateral incisor, and all deciduous teeth in ectopic group and their mean values in Ono's and Otsubo's studies. 2) There were no significant differences as compared to all parts of the size of the dental arch in ectopic sides with those in the normal sides of same individuals at IIA and IIC of Hellman's developmental stage in dentition. 3) When the sizes of the dental arch in the ectopic group were compared with those of the normal group, the former were smaller at the distance between the mid-point and the canine mesial surface (Fig. 1-4), the ridge of the posterior region of the basal arch and most distal point of the primary second molar (Fig. 1-6) at the Hellman's dental age IIA, while the canine distance to the midline (Fig. 1-1), the dental arch perimeter from mid-point to the distal surface of primary second molar (Fig. 1-4+5), and the distance between the canine and primary second molar, div. X (Fig. 1-7) at Hellman's dental age of IIC were significantly smaller than the latter. 4) Regarding the comparison of the value of the changes in dental arch size between the ectopic group and the normal group from Hellman's dental age of IIA to IIC, the distance between the canine and primary second molar, div. X (Fig. 1-7) decreased markedly and the distance between the ridge of the posterior region of the basal arch and the most distal point of the primary second molar (Fig. 1-6) increased. 5) Results of the analysis of X-ray lateral cephalograms showed that the angle of eruption of first molars in the ectopic group was significantly smaller compared with normal group. 6) According to the cluster analysis on the calcification of tooth germ using panoramic radiographs, similarity among all of the samples was lacking in the ectopic group, especially congenital missing of the second molars and second premolars in the ectopic side and the delayed calcification of the ectopically erupted teeth were found in maxilla.

Child↗

PubMed1980

[The journal "Stomatologija (Moskva)"--organ of the medico-scientific all-union Society of Stomatologists of the Soviet Union. Synopsis II].

The present synopsis of the contents of the 1974 volume of the "Stomatologija (Moskva)" treats exclusively problems of surgical stomatology. It considers papers on maxillofacial traumatopathies, fracture surgery, transplantation of teeth and tooth germs, inflammatory diseases, certain surgical-stomatological diseases and neoplasms, bone grafting, extraction surgery and related surgical interventions, and treatment of congenital defects in the maxillofacial region. The synopsis III (1974) (to be published in the next number of the Stomatologie der DDR) will report on further branches of surgical stomatology.

Bone Transplantation↗

PubMed1987

Histology and microradiography of early post-natal molar tooth development in vitamin-D deficient rats.

The role of vitamin D on tooth-germ development was studied. The molars of vitamin D-deficient rats were compared with those of vitamin D-replete controls. The deficiency disturbed enamel and dentine mineralization and decreased their matrix secretion. Morphogenesis was affected; teeth were flattened and the whole of the epithelio-mesenchymal junction rippled. Where this irregularity was maximal, the inner dental epithelium and stratum intermedium were intermingled and the adjoining sub-odontoblast cells were mixed with poorly polarized odontoblasts. The cytodifferentiation of both central and sub-odontoblastic cells was inhibited. Thus vitamin D has a role in the early events of tooth development: morphogenesis, histodifferentiation and cytodifferentiation of pulp cells as well as in enamel and dentine mineralization.

Animals↗

PubMedDate not supplied

The treatment of fusion and supernumerary maxillary central incisors: a case report.

Changes in tooth form may result from heredity, disease, or trauma. Fusion is a union of one or more teeth during development. Gemination means that two separate morphological units are created by division of the tooth germ. Many studies have attempted to discuss the prevalence of double teeth (fusion and gemination) among the persons tested by examining gender, distribution (maxilla or mandible), and whether the anomaly occurred bilaterally or unilaterally. This article describes a case in which one individual was diagnosed with both a supernumerary maxillary central incisor and fusion of a maxillary central incisor.

Child↗

PubMed1996

Regionalized expression of the Dbx family homeobox genes in the embryonic CNS of the mouse.

Here we report the identification of a novel homeobox gene family Dbx in mouse, which consists of Dbx and Dbx2. The two genes share similar structural organization and are encoded by different chromosomes. The predicted Dbx and Dbx2 proteins share 85% identity in their homeodomain amino acid sequences, but otherwise showed no significant similarity. Characterization of the expression of these two genes in the embryos suggested their role in the development of the CNS. In the forebrain, Dbx is expressed in various regions, while Dbx2 showed a more restricted pattern of expression. In the midbrain, the expression domains of Dbx and Dbx2 overlap along the dorso-lateral wall of the ventricle. In the hindbrain and spinal cord, both genes are expressed in the boundary separating the basal and alar plates, which seems to correspond to the sulcus limitans. Expression of the Dbx/Dbx2 genes is restricted to the ventricular region of the embryonic CNS except for that of Dbx in the septum of the telencephalon. Together these observations indicate possible participation of the members of the Dbx family in regionalization of the CNS. While the expression of Dbx was restricted to the CNS, Dbx2 was also expressed in some of the mesenchymal cells, such as limb buds and tooth germs.

Amino Acid Sequence↗

PubMed1995

Regulation of organogenesis. Common molecular mechanisms regulating the development of teeth and other organs.

Vertebrate organs develop from epithelial and mesenchymal tissues, and during their early development they share common morphological features. These include condensation of the mesenchymal cells and thickening, folding or branching of epithelial sheets. Sequential and reciprocal interactions between the epithelial and mesenchymal tissues play central roles in regulation of the morphogenesis of all organs. During recent years increasing amounts of molecular data have accumulated from studies describing developmental changes in expression patterns of molecules, as well as from functional in vitro studies and from the generation of transgenic mice. In this review article, we discuss common features in the molecular regulation that appear to be shared by the developing tooth and other organs. Several growth factors have been shown to act as inductive signals mediating epithelial-mesenchymal interactions in different organs. The early signals are proposed to regulate the expression of master regulatory genes, such as transcription factors. In early tooth germ, bone morphogenetic proteins BMP-2 and BMP-4 regulate expression of the homeobox containing genes Msx-1 and Msx-2. These may specify early patterning of organs through regulation of molecules at the cell surface and the extracellular matrix, such as syndecan-1 and tenascin. Changes in cell adhesion and matrix remodelling, particularly in the organ-specific mesenchyme and in basement membrane contribute to formation of mesenchymal cell condensations and to epithelial morphogenesis. Several growth factors and their receptors, particularly in the TGF beta-, FGF- and EGF- families, have been implicated in formation of mesenchymal condensates and in epithelial morphogenesis of many organs, including the tooth. It is apparent that molecules which regulate morphogenesis in different organs are potential candidate genes for congenital malformation syndromes in which several organs are affected.

Animals↗

PubMed2003

Expression of bone morphogenetic proteins and Msx genes during root formation.

Like crown development, root formation is also regulated by interactions between epithelial and mesenchymml tissues. Bone morphogenetic proteins (BMPs), together with the transcription factors Msx1 and Msx2, play important roles in these interactions during early tooth morphogenesis. To investigate the involvement of this signaling pathway in root development, we analyzed the expression patterns of Bmp2, Bmp3, Bmp4, and Bmp7 as well as Msx1 and Msx2 in the roots of mouse molars. Bmp4 was expressed in the apical mesenchyme and Msx2 in the root sheath. However, Bmps were not detected in the root sheath epithelium, and Msx transcripts were absent from the underlying mesenchyme. These findings indicate that this Bmp signaling pathway, required for tooth initiation, does not regulate root development, but we suggest that root shape may be regulated by a mechanism similar to that regulating crown shape in cap-stage tooth germs. Msx2 expression continued in the epithelial cell rests of Malassez, and the nearby cementoblasts intensely expressed Bmp3, which may regulate some functions of the fragmented epithelium.

Animals↗

PubMed1989

[Consideration on the treatment of transposition of the teeth].

The two cases with the transposition of the teeth were treated orthodontically. One was a case in which the teeth which had changed places with each other were aligned in irregular sequence, the other was one with the teeth which had erupted at the unusual position were repositioned in order of the tooth number. Those causes and some problems involved in diagnosis and treatment were discussed. 1. The causes of transposition of the teeth in the two cases reported herein seemed to be premature loss of primary teeth and the malposition of permanent tooth germs, respectively. 2. At the time of the planning of the treatment, the following must be considered. 1) Perfect transposition or imperfect. 2) The positions of root apexes and axial inclinations of the teeth irregularly erupted. 3. Root paralleling is most important for the stability of the treatment results. Moreover, in case of unusual alignment, prevention of premature contact in jaw movement and improvement of appearance must be endeavored.

Humans↗

PubMed1994

Stimulation of DNA synthesis by endothelin-1 in primary cultures of human dental pulp.

Endothelin (ET), besides being a powerful vasoactive agent, acts as a mitogen in some cell types. ET-like immunoreactivity has been recently detected by immunocytochemistry in the vascular endothelium of human tooth germ and dental pulp, thus providing evidence for local ET production in these tissues. The effects of ET-1 on DNA synthesis in primary cultures of human dental pulp were now investigated. DNA synthesis was evaluated by flow cytometric assay and by 5-bromo,2'deoxyuridine incorporation as detected by immunocytochemistry. Cultured cells were morphologically similar to dental pulp cells and displayed vimentin immunoreactivity. Incubation of cultures with ET-1 resulted in a dose-dependent increase in the number of S-phase-traversing cells over control (unstimulated) cultures. Control skin fibroblasts were also responsive to ET. This finding raises the possibility that the multifunctional peptide ET-1 might subserve growth-promoting activity in the human tooth. It is tentatively suggested that such as an activity might be important during tooth development and in pulp inflammation and healing.

Adolescent↗

PubMed2004

Runx2 mediates FGF signaling from epithelium to mesenchyme during tooth morphogenesis.

Runx2 (Cbfa1) is a runt domain transcription factor that is essential for bone development and tooth morphogenesis. Teeth form as ectodermal appendages and their development is regulated by interactions between the epithelium and mesenchyme. We have shown previously that Runx2 is expressed in the dental mesenchyme and regulated by FGF signals from the epithelium, and that tooth development arrests at late bud stage in Runx2 knockout mice [Development 126 (1999) 2911]. In the present study, we have continued to clarify the role of Runx2 in tooth development and searched for downstream targets of Runx2 by extensive in situ hybridization analysis. The expression of Fgf3 was downregulated in the mesenchyme of Runx2 mutant teeth. FGF-soaked beads failed to induce Fgf3 expression in Runx2 mutant dental mesenchyme whereas in wild-type mesenchyme they induced Fgf3 in all explants indicating a requirement of Runx2 for transduction of FGF signals. Fgf3 was absent also in cultured Runx2-/- calvarial cells and it was induced by overexpression of Runx2. Furthermore, Runx2 was downregulated in Msx1 mutant tooth germs, indicating that it functions in the dental mesenchyme between Msx1 and Fgf3. Shh expression was absent from the epithelial enamel knot in lower molars of Runx2 mutant and reduced in upper molars. However, other enamel knot marker genes were expressed normally in mutant upper molars, while reduced or missing in lower molars. These differences between mutant upper and lower molars may be explained by the substitution of Runx2 function by Runx3, another member of the runt gene family that was upregulated in upper but not lower molars of Runx2 mutants. Shh expression in mutant enamel knots was not rescued by FGFs in vitro, indicating that in addition to Fgf3, Runx2 regulates other mesenchymal genes required for early tooth morphogenesis. Also, exogenous FGF and SHH did not rescue the morphogenesis of Runx2 mutant molars. We conclude that Runx2 mediates the functions of epithelial FGF signals regulating Fgf3 expression in the dental mesenchyme and that Fgf3 may be a direct target gene of Runx2.

Animals↗