Excess NF-κB induces ectopic odontogenesis in embryonic incisor epithelium.

Nuclear factor kappa B (NF-κB) signaling plays critical roles in many physiological and pathological processes, including regulating organogenesis. Down-regulation of NF-κB signaling during development results in hypohidrotic ectodermal dysplasia. The roles of NF-κB signaling in tooth development, however, are not fully understood. We examined mice overexpressing IKKß, an essential component of the NF-κB pathway, under keratin 5 promoter (K5-Ikkß). K5-Ikkß mice showed supernumerary incisors whose formation was accompanied by up-regulation of canonical Wnt signaling. Apoptosis that is normally observed in wild-type incisor epithelium was reduced in K5-Ikkß mice. The supernumerary incisors in K5-Ikkß mice were found to phenocopy extra incisors in mice with mutations of Wnt inhibitor, Wise. Excess NF-κB activity thus induces an ectopic odontogenesis program that is usually suppressed under physiological conditions.

An idiosyncratic post-traumatic tetrad: compound odontome, dentigerous cyst, impaction, and double-dilaceration.

OBJECTIVE: This report describes the case of a 13-year-old patient who experienced traumatic intrusion of the primary maxillary right central incisor and subsequently suffered an atypical tetrad, comprising of an unerupted compound odontoma associated with a dentigerous cyst, and an impacted, doubly dilacerated permanent maxillary right central incisor; however, the high interconnectivity of the occurrence of four pathologies together is unusual has not previously been reported. SUMMARY: The pathologies were detected 7 years after trauma; surgical removal of odontome along with the dentigerous cyst was performed, followed by orthodontic extrusion of the impacted double-dilacerated permanent central incisor. The 18-month follow-up shows no pathology, no gingival recession, and normal probing depth.

YAP overexpression affects tooth morphogenesis and enamel knot patterning.

Teeth develop through distinct morphological stages. At the cap stage, a compactly clustered and concentrically arranged cell mass, the enamel knot, appears at the tip of the enamel organ. Cells in this knot express sets of key molecules, and as such have been proposed to act as a signaling center directing tooth morphogenesis and tooth cusp formation. YAP is a transcriptional co-activator of the Hippo signaling pathway that is essential for the proper regulation of organ growth. In this study, we analyzed the tooth phenotype in transgenic mice that overexpressed a constitutively active form of YAP in the dental epithelium. We found that overexpression of YAP resulted in deformed tooth morphogenesis with widened dental lamina. In addition, the enamel knot was mislocated to the upper portion of the enamel organ, where it remained devoid of proliferating cells and contained apoptotic cells with intense Edar transcripts and reduced E-cadherin expression. Interestingly, some signaling molecules, such as Shh, Fgf4, and Wnt10a, were not expressed in this mislocated enamel knot, but remained at the tip of the enamel organ. Analysis of these data suggests that the signaling center is induced by reciprocal epithelial-mesenchymal interactions, and its induction may be independent of the enamel knot.

Single tooth odontodysplasia. Case report.

Odontodysplasia (ghost tooth) is an uncommon, nonhereditary developmental condition of unknown origin, affecting both mesodermal and ectodermal elements of the dental organ. To our knowledge, this case is unique in that it is only the second reported case of odontodysplasia affecting a single tooth. Based on clinical, radiographic and histologic findings, we diagnosed this tooth as a ghost tooth.

Regional odontodysplasia. A literature review and three case reports.

AIM: The purpose of this article is to report some unusual characteristics related to gender, location and manifestations of severe Regional Odontodysplasia detected in three subjects. Regional Odontodysplasia is a rare disturbance of dental development whose aetiology is still unknown. Anomalies involve enamel, dentin, pulp and dental follicle causing atypical structure, colour, shape, size and eruptive disturbances of the affected teeth. Its early onset may lead to craniofacial development disturbances. CASES REPORTS: This article reports three cases with unusual characteristics observed in male children who were assisted by a paediatric dentist. Generally the disease affects one hemiarch and it is very rare that it crosses the midline as in one of the presented cases. Regional Odontodysplasia has been predominantly described in the maxilla and in women, however these three cases are in boys and two of them occured in the mandible. CONCLUSION: Regional Odontodysplasia is a rare disease, causing severe dental, growing and craniofacial development anomalies. Treatment needs to be personalised, aiming at preservation of the affected teeth taking into account their risk to develop severe infections. Parents should be made aware of the need for an extensive follow-up.

Dental Findings and Management in a Mucopolysaccharidosis Type IIIB Patient.

Mucopolysaccharidosis type IIIB (MPS IIIB) is an autosomal recessive disorder caused by deficiency of the lysosomal enzyme a-N-acetylglucosaminidase. Affected subjects present developmental delay, attention deficit disorder, uncontrollable hyperactivity, and aggressive behavior, followed by progressive dementia and death in late adolescence. The purpose of this paper is to report the dental findings and treatment in a child with MPS IIIB. His primary molars and permanent mandibular incisors presented obliterated pulp chambers and root canals, which may be a clinical manifestation of this disorder.

Histological and immunohistochemical analyses of molar tooth germ in enamelin-deficient mouse.

Amelogenesis imperfecta (AI) is associated with mutations in a number of genes, including AMELX and ENAM. However, the precise mechanism leading to enamel malformation in different AI types remains to be elucidated. In the present study, we investigated morphological change in tooth germ obtained from ENAM-mutant mice (Enam(Rgsc521) homozygotes) as a model for human AI using histological and immunohistochemical methodologies. The results showed that ameloblasts detached from developing dentin and lost cell polarity in mutant mice at post-natal day 3. Cyst-like structures, including amelogenin-immunopositive materials, were observed between these detached cells and the dentin. No enamel-like structure, however, was observed in the cusp of the crown. These results suggest that enamelin acts as an adhesion molecule and is involved in ameloblast cell differentiation during the early stages of tooth development.

Aberrant cementum phenotype associated with the hypophosphatemic hyp mouse.

BACKGROUND: Cementogenesis is sensitive to altered local phosphate levels; thus, we hypothesized a cementum phenotype, likely of decreased formation, would be present in the teeth of X-linked hypophosphatemic (Hyp) mice. Mutations in the phosphate-regulating gene with homologies to endopeptidases on the X chromosome (Phex) cause X-linked hypophosphatemia, characterized by rickets, osteomalacia, and hypomineralized dentin formation, a phenotype recapitulated in the Hyp mouse homolog. Here, we report a developmental study of tooth root formation in Hyp mouse molars, focusing on dentin and cementum. METHODS: Light and transmission electron microscopy were used to study molar tissues from wild-type (WT) and Hyp mice. Demineralized and hematoxylin and eosin-stained tissues at developmental stages 23 to 96 days postcoital (dpc) were examined by light microscopy. Immunohistochemistry methods were used to detect bone sialoprotein (BSP) distribution in Hyp and WT mouse molar tissues, and transmission electron microscopy was used to study similar molar tissues in the non-demineralized state. RESULTS: Dentin in Hyp mice exhibited mineralization defects by 33 dpc, as expected, but this defect was partially corrected by 96 dpc. In support of our hypothesis, a cementum phenotype was detected using a combination of immunohistochemistry and transmission electron microscopy, which included thinner BSP-positive staining within the cementum, discontinuous mineralization, and a globular appearance compared to WT controls. CONCLUSION: Mutations in the phosphate-regulating Phex gene of the Hyp mouse resulted in defective cementum development.

Irrupção ectópica de incisivo lateral inferior: relato de caso / Ectopic eruption of a mandibular lateral incisor: relate of case

A transposição dentária constitui uma rara e severa anomalia de desenvolvimento, sendo considerada um dos tipos de irrupção ectópica na qual dois dentes permanentes trocam de posição no arco. Este trabalho dis cuteas diferentes abordagens em casos de transposições existentes na literatura, bem como relata um caso clínico em que uma irrupção ectópica de incisivo lateralinferior foi interceptada a fim de evitar uma futura transposição incisivo lateral-canino

Radiographic evaluation of the fate of developing tooth buds on the fracture line of mandibular fractures.

PURPOSE: The goal was to suggest guidelines for the treatment of developing tooth buds located on the fracture line of mandibular fractures. PATIENTS AND METHODS: The long-term radiographic follow-up records of 28 patients with mandibular fractures involving 66 tooth buds were examined for the occurrence of abnormalities in development or eruption. The fates of the involved teeth were compared according to the fracture conditions and other factors, and the cause of the abnormalities was surveyed. RESULTS: Abnormal findings were observed in 30 of 66 developing teeth (45%); these included deficient root formation, abnormal bend of the root, nodule formation on the root, partial obliteration of the pulp cavity, impaction, growth arrest, and external resorption. No relationship was found between the presence of abnormalities and the condition of the fracture or the developmental stage of the tooth buds. However, infection, rotation of the tooth bud, and a surgical wire passing through the follicular space were associated with arrested growth and impaction. CONCLUSIONS: The tooth buds present on the fracture line should be preserved except in cases of infection, and careful attention should be paid to avoiding further injury to the tooth bud and the soft tissues of the follicle at the time of surgery.

[Effect of the Tabby mutation on the dentition of mice]. / Effets de la mutation Tabby sur la dentition chez la souris.

The X-linked hypohidrotic ectodermal dysplasia in man leads to dental defects and is homologous to the Tabby (Ta) mutation in mouse. We currently investigate the effects of the Ta mutation on odontogenesis. The incisor germ of Ta showed an abnormal size and shape, a change in the balance between prospective crown- and root-analogue tissues and retarded cytodifferentiation. Although the enamel organ in Ta incisors was smaller, a larger proportion of the dental papilla was covered by preameloblasts-ameloblasts. The independent development of the labial and lingual parts of the enamel organ in rodent lower incisor might reflect their heterogeneous origin, as demonstrated for the upper incisor. The mandibular cheek dentition in Ta mice exhibits large variations classified in five morphotypes, based on the tooth number, shape, size and position. In Ta embryos, the mesio-distal extent of the dental epithelium was similar to that in WT, but its segmentation was altered. These morphotypes could be explained by a tentative model suggesting that 1) the positions of tooth boundaries differ in Ta and WT molars and among the Ta morphotypes; 2) the tooth patterns are determined by the distal boundary of the most mesial tooth primordium while the distal teeth take advantage of the remaining dental epithelium; 3) one tooth primordium in Ta mice might derive from adjacent parts of two primordia in WT.

Abnormal epidermal differentiation and impaired epithelial-mesenchymal tissue interactions in mice lacking the retinoblastoma relatives p107 and p130.

The functions of p107 and p130, members of the retinoblastoma family, include the control of cell cycle progression and differentiation in several tissues. Our previous studies suggested a role for p107 and p130 in keratinocyte differentiation in vitro. We now extend these data using knockout animal models. We found impaired terminal differentiation in the interfollicular keratinocytes of p107/p130-double-null mice epidermis. In addition, we observed a decreased number of hair follicles and a clear developmental delay in hair, whiskers and tooth germs. Skin grafts of p107/p130-deficient epidermis onto NOD/scid mice showed altered differentiation and hyperproliferation of the interfollicular keratinocytes, thus demonstrating that the absence of p107 and p130 results in the deficient control of differentiation in keratinocytes in a cell-autonomous manner. Besides normal hair formation, follicular cysts, misoriented and dysplastic follicles, together with aberrant hair cycling, were also observed in the p107/p130 skin transplants. Finally, the hair abnormalities in p107/p130-null skin were associated with altered Bmp4-dependent signaling including decreased DeltaNp63 expression. These results indicate an essential role for p107 and p130 in the epithelial-mesenchimal interactions.

Different morphotypes of functional dentition in the lower molar region of tabby (EDA) mice.

OBJECTIVES: To sort and classify the highly variable lower molar dentition in tabby (Ta) mice postnatally. The Ta syndome is homologous to the anhidrotic (hypohidrotic) ectodermal dysplasia (EDA) in human and includes severe developmental defects of teeth, hair and sweat glands. DESIGN: Analysis of tooth shape and cusp pattern and measurement of the mesio-distal crown length. SETTING AND SAMPLE POPULATION: Institute of Experimental Medicine, Academy of Sciences, Prague. Fixed heads of 107 tabby (Ta) homozygous and hemizygous mice and 90 wild type mice aged from post-natal day 11 to adulthood, collected during 1995-2001. OUTCOME MEASURE: Identification of distinct morphotypes of Ta dentition. Reduced tooth length in Ta teeth and specific differences in tooth length between distinct morphotypes. RESULTS: The variable dentitions in the lower molar region of Ta mice were classified in two basic morphotypes I and II. The morphotype I was further subdivided into particular morphotypes Ia, Ib and Ic. Proportion of the basic morphotypes I and II was different in the offspring of heterozygous (84% and 12%) compared with homozygous + hemizygous (45% and 52%) mothers. The proportions of particular morphotypes within a basic morphotype were similar in both offspring groups. CONCLUSION: The identification of the distinct morphotypes made possible to classify the structural variability of the mandibular functional dentition in Ta mice.

Different morphotypes of the tabby (EDA) dentition in the mouse mandible result from a defect in the mesio-distal segmentation of dental epithelium.

OBJECTIVES: Prenatal identification of the different dentition morphotypes, which exist in the lower molar region of tabby (Ta) adult mice, and investigation of their origin. The mouse Ta syndrome and its counterpart anhidrotic (hypohidrotic) ectodermal dysplasia (EDA) in human are characterized by absence or hypoplasia of sweat glands, hair and teeth. DESIGN: Analysis of tooth morphogenesis using serial histological sections and 3D computer aided reconstructions of the dental epithelium in the cheek region of the mandible. SETTING AND SAMPLE POPULATION: Institute of Experimental Medicine, Academy of Sciences, Prague. Heads of 75 Ta homozygous and hemizygous mice and 40 wild type (WT) control mice aged from embryonic day (ED) 14.0-20.5 (newborns), harvested during 1995-2001. OUTCOME MEASURE: Prenatal identification of five distinct morphotypes of Ta dentition on the basis of differences in tooth number, size, shape, position and developmental stage and of the morphology of the enamel knot in the most mesial tooth primordium. RESULTS: The mesio-distal length of the dental epithelium was similar in the lower cheek region in Ta and WT mice. In Ta embryos, there was altered the mesio-distal segmentation of the dental epithelium giving rise to the individual tooth primordia. Prenatally, two basic morphotypes I and II and their particular subtypes (Ia, Ib, Ic, and IIa, IIb, respectively) of the developing dentition were identified from day 15.5. The incidence of the distinct morphotypes in the present sample did not differ from postnatal data. The proportion of the morphotype I and II was dependent on mother genotype. CONCLUSION: The different dentition morphotypes in Ta mice originate from a defect in the mesio-distal segmentation of the dental epithelium in mouse embryos. This defect presumably leads to variable positions of tooth boundaries that do not correspond to those of the WT molars. One tooth primordium of Ta mice might be derived from adjacent parts of two molar primordia in WT mice.

Disturbed tooth eruption in osteopetrotic (op/op) mice: histopathogenesis of tooth malformation and odontomas.

BACKGROUND: Odontoma-like structures are formed in the jaw bone of osteopetrotic (op/op) mice, which have a congenital deficiency in osteoclastic differentiation due to the absence of functional macrophage colony-stimulating factor (M-CSF). METHODS: To clarify the histopathogenesis of tooth malformation and odontoma-like structures, a 2-year postnatal process of development of the op/op mandibular incisor was examined radiologically and histologically. At the same time, extracellular matrix (ECM) remodeling around tooth germs was analyzed immunohistochemically. RESULTS: Abnormal forms of op/op tooth germ were noticeable even at 3 days after birth on a radiogram. Histologically, op/op mice were clearly distinguished by the disappearance of dental follicular space at 3 days. With aging, bone trabeculae, which were not remodeled, penetrated into op/op tooth germs and divided them into several daughter germs, which were recognized as odontomas. In mandibular incisor bodies, the immature ECM components, such as heparan sulfate proteoglycan and tenascin, were preserved diffusely in the dental papilla/pulp, which indicates that maturation of the stroma does not take place in op/op mandibular incisors. CONCLUSION: The observation suggests that the disturbed morphogenesis of op/op tooth germs is functionally explained by the disordered immunolocalization of ECM molecules, and that the dental follicular space is essential for normal tooth development because it prevents bone penetration into the tooth germs.

No developmental failure of cultured tooth germs from osteopetrotic (op/op) mice.

BACKGROUND: Incisor tooth germs of osteopetrotic (op/op) mice are known to fail to erupt, but form odontomas in their root apices instead, due to invasion of alveolar bone trabeculae into the tooth germs. The purpose of this study is to determine if the tooth developmental failures in op/op mice are intrinsic or secondarily arise as a result of the defective bone metabolism due to lack of macrophage colony-stimulating factor (M-CSF). METHODS: We isolated mandibular first molar tooth germs from normal and op/op mice and cultured them under conditions with or without bone tissues which had been formed around tooth germs. RESULTS: Tooth germs from normal mice, cultured for a week, showed almost the same developmental features as those of mice with the corresponding age. They were surrounded with dental follicular tissues and were never invaded by bone trabeculae. On the other hand, op/op tooth germs cultured in the presence of bone components were invaded by alveolar bone trabeculae around tooth germs in the same manner as shown in vivo. When cultured without bone, they developed without any interruptions. CONCLUSIONS: These findings indicated that op/op tooth germs had potential for normal development and that their abnormal development was a secondary phenomenon caused by lack of bone remodeling in the early phase of odontogenesis.

The dentofacial manifestations of XXXXY syndrome: a case report.

This paper presents a six-year-old patient with XXXXY syndrome, whose oral findings included a cleft soft palate, hyper- or meso-taurodontism in eight primary molars and in the mandibular permanent first molars, five congenitally missing premolars, and delayed development of the permanent tooth germs. The maxillary and mandibular primary central incisors were in a cross-bite relationship. Cephalometric findings showed a short ramus of the mandible and a short maxilla in the anterioposterior plane. The anteroposterior jaw relationship was in harmony. The cross-bite was considered to be due to the retroinclination of the maxillary primary incisors. This case emphasises the importance of regular dental care, and monitoring of facial growth and dental development in children with XXXXY syndrome.

Simultaneous occurrence of unusual odontodysplasia and oligodontia in the permanent dentition: report of a case.

Odontodysplasia is an uncommon clinicopathological condition with a variety of expressions. Although it is generally recognized as a localized disorder of dental tissue, its aetiology has not yet been well explained. In the present case, odontodysplasia with oligodontia in the permanent dentition is reported. The patient was in good health with normal stature and no other physical abnormalities. His parents and siblings were dentally and medically normal. The primary teeth appeared to be normal except for the primary second molars, where the enamel was malformed. However, the permanent incisors that had erupted into the oral cavity showed rough and hypoplastic enamel. An orthopantomogram showed 17 congenitally missing permanent teeth and malformation of the other 11 permanent teeth and tooth-germs. Because these findings were caused by developmental disturbances of both the mesodermal and ectodermal dental components, we diagnosed the present case as odontodysplasia accompanied by oligodontia in the permanent dentition.

A review of 47 cases of unerupted maxillary incisors.

OBJECTIVES: To study the prevalence of aetiological factors associated with unerupted maxillary incisors and to follow the outcome of treatment in a study of 47 cases. DESIGN: A retrospective study. SETTING: The Dental Department, St Luke's Hospital, Malta, the School Dental Clinic of Malta and the private practices of two orthodontists in Malta. SAMPLE AND METHODS: Forty-seven patients with a total of 53 unerupted maxillary incisors were classified according to the aetiological factors causing non-eruption. The relative prevalence of the various aetiologies were ascertained, and the outcome after treatment was recorded to assess the efficacy of the treatment methods being used. RESULTS: The most common cause of lack of eruption was the presence of supernumerary teeth (47% of patients). The other 53% of cases were distributed more or less equally between the remaining aetiological factors, which were odontomes (9%), dilacerations (9%), tooth germ malposition (12%), crowding (4%), one case of a calcifying odontogenic cyst (2%) and one case of trauma to the preceding deciduous tooth (2%). The aetiology of 15% of cases could not be ascertained. Once supernumerary teeth were removed, maxillary incisors usually erupted successfully with the help of conventional treatment methods such as surgical exposure and orthodontics. A relatively large number of incisors that failed to erupt due to other aetiological factors had to be extracted. CONCLUSIONS: Maxillary incisors that fail to erupt due to the presence of supernumerary teeth have a better prognosis than unerupted incisors with less common aetiologies.