Giant Complex Odontoma of Mandible: A Spectacular Case Report.
ABSTRACT: Odontomas are considered as benign tumors of odontogenic tissue origin and are more over non-aggressive. They can also be categorized as hamartomas and are a result of developmental malformation of odontogenic tissues. As the name suggests, they are composed of mature tooth substances. They possess limited and slow growth potential and are well differentiated. They can be ectodermal, mesodermal or mixed in origin. Mixed variety may be further divided into compound or complex depending upon their radio-graphical resemblance to the tooth. Compound odontomes are reported to be twice more common than complex odontomes. Among them, complex odontomes are asymptomatic unless they cause bony expansion of the jaws.This paper aims to report and discuss a case of complex odontoma with unusually large size leading to gross facial asymmetry. Further this paper will highlight the important information the general dental practitioner must possess to diagnose such lesions at an early stage.Odontomas are benign odontogenic tumors with unusually large size leading to gross facial asymmetry. The general dental practitioners must possess the knowledge and important information to diagnose such lesions at an early stage.
Project description:Regenerating human tooth ex vivo and biological repair of dental caries are hampered by non-viable odontogenic stem cells that can regenerate different tooth components. Odontoma is a developmental dental anomaly that may contain putative post-natal stem cells with the ability to differentiate and regenerate in vivo new dental structures that may include enamel, dentin, cementum and pulp tissues. We evaluated odontoma tissues from 14 patients and further isolated and characterized human odontoma-derived mesenchymal cells (HODCs) with neural stem cell and hard tissue regenerative properties from a group of complex odontoma tissues from 1 of 14 patients. Complex odontoma was more common (9 of 14) than compound type and females (9 of 14) were more affected than males in our set of patients. HODCs were highly proliferative like dental pulp stem cells (DPSCs) but demonstrated stronger neural immunophenotype than both DPSCs and mandible bone marrow stromal cells (BMSCs) by expressing higher levels of nestin, Sox 2 and betaIII-tubulin. When transplanted with hydroxyapatite/tricalcium phosphate into immunocompromised mice, HODCs differentiated and regenerated calcified hard tissues in vivo that were morphologically and quantitatively comparable to those generated by DPSCs and BMSCs. When transplanted with polycaprolactone (biodegradable carrier), HODCs differentiated to form new predentin on the surface of a dentin platform. Newly formed predentin contained numerous distinct dentinal tubules and an apparent dentin-pulp arrangement. HODCs represent unique odontogenic progenitors that readily commit to formation of dental hard tissues.
Project description:A new spontaneous mouse mutant (ntl) with autosomal-recessive osteopetrosis was characterized. These mice formed tartrate-resistant acid phosphate (TRAP)-positive osteoclasts but their osteoclasts had no ruffled border and did not resorb bone. These mice displayed no tooth eruption or tooth root formation. Adult mutant mice developed odontoma-like proliferations near the proximal ends of the incisors. Intraperitoneal injection of progenitor cells from the liver of 16.5 days postcoitum wild-type embryos into newborn mutants rescued the osteopetrosis phenotype, indicating that the defects were intrinsic to the osteoclasts. Our findings not only provide further support for a critical role of osteoclasts in tooth eruption and tooth root development, but also suggest that the perturbation of the homeostasis of the odontogenic precursors of the incisors is primarily responsible for the development of the odontoma-like proliferations in this osteopetrosis mutant. Genetic mapping has narrowed down the location of the mutant allele to a genetic interval of 3.2 cM on mouse chromosome 17.
Project description:Tooth pain is a common presentation in primary care, with 32.4% of Singaporeans experiencing pain from dental caries in their lifetime. Some systemic conditions can have oral presentations, and oral conditions may be associated with chronic disease. A good history and examination is key in delineating odontogenic from non-odontogenic causes of tooth pain. Primary care physicians should accurately diagnose and assess common dental conditions and make appropriate referrals to the dentist. Common non-odontogenic causes of orofacial pain can be mostly managed in primary care, but important diagnoses such as acute coronary syndrome, peritonsillar abscess and temporal arteritis must not be missed. Ibuprofen has been shown to be effacious, safe and cost-effective in managing odontogenic pain. Antibiotics are indicated when there is systemic or local spread of dental infection. Without evidence of spread, antibiotics have not been shown to reduce pain or prevent subsequent dental infections.
Project description:Odontomas are the most common odontogenic hamartomas worldwide. Depending on the level of organisation of the tissues inside, these can be differentiated into compound type or complex type. As these are asymptomatic and do not cause any changes in the bone, they are often diagnosed during the routine dental examination. Complex odontomas are commonly found to occur in posterior mandible while compound odontomas are found in the anterior maxilla. A nine-year-old female child reported for a routine dental check-up, when a missing left permanent mandibular lateral incisor  was noticed. Further investigations revealed compound odontoma and unerupted 32, which is an unusual location. Early detection of these tumours is essential to avoid lengthy corrective treatments.
Project description:Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant or spontaneous disorder characterized by multiple cutaneous basal cell carcinomas, odontogenic keratocysts, skeletal anomalies and facial dysmorphology, including cleft lip and palate. Causative mutations for NBCCS occur in the PTCH1 gene on chromosome 9q22.3-q31, which encodes the principle receptor for the Hedgehog signalling pathway. We have investigated the molecular basis of craniofacial defects seen in NBCCS using a transgenic mouse model expressing Shh in basal epithelium under a Keratin-14 promoter. These mice have an absence of flat bones within the skull vault, hypertelorism, open-bite malocclusion, cleft palate and arrested tooth development. Significantly, increased Hedgehog signal transduction in these mice can influence cell fate within the craniofacial region. In medial edge epithelium of the palate, Shh activity prevents apoptosis and subsequent palatal shelf fusion. In contrast, high levels of Shh in odontogenic epithelium arrests tooth development at the bud stage, secondary to a lack of cell proliferation in this region. These findings illustrate the importance of appropriately regulated Hedgehog signalling during early craniofacial development and demonstrate that oro-facial clefting and hypodontia seen in NBCCS can occur as a direct consequence of increased Shh signal activity within embryonic epithelial tissues.
Project description:Stem cell-based developmental engineering has been considered as a promising strategy for tissue/organ regeneration. Tooth is formed by sequential reciprocal interactions between epithelium derived from surface ectoderm and mesenchymal cells derived from cranial neural crest. The neural crest cell is an appealing cell source for tooth development and regeneration research. In this study, we investigated the odontogenic differentiation and dentin-pulp complex regeneration potential of neural crest cells. Our results showed that neural crest cells (O9-1 mouse cranial neural crest cell line) can sequentially differentiate into dentin matrix acidic phosphoprotein 1 (DMP-1)-positive odontoblasts within a developing tooth germ in vitro. Moreover, O9-1 cells and induced pluripotent stem cell (iPSC)-derived neural crest-like cells (iNCLCs) can form well-organized vascularized dentin-pulp complex when transplanted in vivo with tooth scaffold. Furthermore, both O9-1 cells and iNCLCs can be differentiated into odontoblast-like cells, positive staining with odontogenic-related markers DMP-1 and dentin sialophosphoprotein (DSPP), under odontogenic induction with the administration of bone morphogenetic protein 4 (BMP-4). These results demonstrated that neural crest cells, especially the unlimited iNCLCs, are a promising cell source for tooth development and dental tissue/tooth organ regeneration studies.
Project description:The surgical treatment of some odontogenic tumors often leads to tooth and maxillary bone loss as well as to facial deformity. Therefore, the identification of genes involved in the pathogenesis of odontogenic tumors may result in alternative molecular therapies. The PRKAR1A gene displays a loss of protein expression as well as somatic mutations in odontogenic myxomas, an odontogenic ectomesenchymal neoplasm. We used a combination of quantitative RT-PCR (qRT-PCR), immunohistochemistry, loss of heterozygosity (LOH) analysis, and direct sequencing of all PRKAR1A exons to assess if this gene is altered in mixed odontogenic tumors. Thirteen tumors were included in the study: six ameloblastic fibromas, four ameloblastic fibro-odontomas, one ameloblastic fibrodentinoma, and two ameloblastic fibrosarcomas. The epithelial components of the tumors were separated from the mesenchymal by laser microdissection in most of the cases. We also searched for odontogenic pathology in Prkar1a(+) (/) (-) mice. PRKAR1A mRNA/protein expression was decreased in the benign mixed odontogenic tumors in association with LOH at markers around the PRKAR1A gene. We also detected a missense and two synonymous mutations along with two 5'-UTR and four intronic mutations in mixed odontogenic tumors. Prkar1a(+) (/) (-) mice did not show evidence of odontogenic tumor formation, which indicates that additional genes may be involved in the pathogenesis of such tumors, at least in rodents. We conclude that the PRKAR1A gene and its locus are altered in mixed odontogenic tumors. PRKAR1A expression is decreased in a subset of tumors but not in all, and Prkar1a(+) (/) (-) mice do not show abnormalities, which indicates that additional genes play a role in this tumor's pathogenesis.
Project description:Over the past 40 years, studies on tooth regeneration have been conducted. These studies comprised two main flows: some focused on epithelial–mesenchymal interaction in the odontogenic region, whereas others focused on creating a supernumerary tooth in the non-odontogenic region. Recently, the scope of the research has moved from conventional gene modification and molecular therapy to genome and transcriptome sequencing analyses. However, these sequencing data have been produced only in the odontogenic region. We provide RNA-Seq data of not only the odontogenic region but also the non-odontogenic region, which loses tooth-forming capacity during development and remains a rudiment. Sequencing data were collected from mouse embryos at three different stages of tooth development. These data will expand our understanding of tooth development and will help in designing developmental and regenerative studies from a new perspective.
Project description:Non-syndromic facial asymmetry is commonly found in dentofacial deformity populations with skeletal malocclusions. Asymmetry of this type may result from imbalanced growth and function of both the jaw and associated muscles. Among the multiple genes that interact to affect the craniofacial musculoskeletal complex during pre and postnatal growth and development, NODAL signaling pathwy (NSP) genes are active in adult skeletal muscle and may be key factors in development, growth and maintenance of facial asymmetry. It is of interest to determine whether expression of NODAL pathway genes might differ in masseter muscles between individuals with malocclusion that have facial asymmetry and normal symmetry. Human Transcriptome 2.0 GeneChips (HTA2.0) were used to examine global gene expression in masster muscles between malocclusion subjects with posterior facial asymmetry and with normal facial symmetry. Eleven patients undergoing orthoganthic surgery were selected for comparison of masseter muscle gene expression on microarrays. Two subjects had posterior facial asymmetry (one with class II open bite and one with class III open bite malocclusion) and nine subjects had normal facial symmetry (three with class II open bite, two with class III open bite and four with class II deep bite malocclusion). RNA representative of total gene expression in masseter muscles of the malocclusion subjects with and without posterior facial asymmetry was prepared for labeling and hybridization on HTA2.0 chips. The two subjects with facial asymmetry clustered separately from eight other malocclusion subjects by a principle component analysis (PCA), even though one had a class II and the other a class III malocclusion. Sample 4L_Open_II is from a subject who has sleep apnea. Data from 4L_Open_II clustered independent of the asymmetry group and the eight other subjects of the symmetry group by PCA and was not included in analysis of differential expression with facial symmetry. Masseter muscles are paired jaw muscles (i.e. right and left masseter). In some cases, there was not sufficient quantity/quality of RNA from one side, thus the other side was used. Please note that the following information is provided in the 'source name' field of each sample record; subject ID number; either left or right masseter; J CRANIOFAC SURG_ID# corresponding to the data presented in the manuscript
Project description:Odontomas, developmental anomalies of tooth germ, frequently occur in familial adenomatous polyposis patients with activated Wnt/?-catenin signaling. However, roles of Wnt/?-catenin signaling in odontomas or odontogenic cells are unclear. Herein, we investigated ?-catenin expression in odontomas and functions of Wnt/?-catenin signaling in tooth germ development. ?-catenin frequently accumulated in nucleus and/or cellular cytoplasm of odontogenic epithelial cells in human odontoma specimens, immunohistochemically. Wnt/?-catenin signaling inhibited odontogenic epithelial cell proliferation in both cell line and tooth germ development, while inducing immature epithelial bud formation. We identified Semaphorin 3A (Sema3A) as a downstream molecule of Wnt/?-catenin signaling and showed that Wnt/?-catenin signaling-dependent reduction of Sema3A expression resulted in suppressed odontogenic epithelial cell proliferation. Sema3A expression is required in appropriate epithelial budding morphogenesis. These results suggest that Wnt/?-catenin signaling negatively regulates odontogenic epithelial cell proliferation and tooth germ development through decreased-Sema3A expression, and aberrant activation of Wnt/?-catenin signaling may associate with odontoma formation.