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Journal of Oral Biosciences Mar 2020The Bone Morphogenetic Proteins (BMPs) direct tooth development and still express in the adult tooth. We hypothesized that inhibition of BMP function would therefore...
OBJECTIVES
The Bone Morphogenetic Proteins (BMPs) direct tooth development and still express in the adult tooth. We hypothesized that inhibition of BMP function would therefore disrupt dentinogenesis by differentiated odontoblasts.
METHODS
We generated mice overexpressing the BMP-inhibitory protein Noggin in differentiated odontoblasts and osteocytes under control of a Dmp1 promoter-driven cre transgene. We compared the dentin phenotype in these mice with that in WT littermates and in mice with a Smad4 odontoblast/osteocyte knockout mediated by the same cre and therefore lacking all BMP and Tgfβ signaling in the same tissues.
RESULTS
Three-month-old first molars from both Noggin-expressing and Smad4-deleted mice showed decreased dentin volume with enlarged pulp cavities, and both displayed less organized and mineralized dentinal tubules compared to WT. The Smad4-ablated phenotype was more severe. While dentin sialophosphoprotein (DSPP) and bone sialoprotein (BSP) were decreased in the dentin of both lines, dentin matrix protein 1 (DMP1) was sharply increased in Noggin-expressing teeth.
CONCLUSIONS
The phenotypes we observed in Noggin-overexpressing and Smad4-conditional knockout teeth resemble the phenotype of Dentinogenesis Imperfecta (DGI) type III. Our results show that BMPs regulate post-natal dentinogenesis and that BMP-inhibitory proteins like Noggin play a role in that regulation. The increased severity of the Smad4 phenotype indicates that Tgfβ ligands, in addition to BMPs, play a crucial role in post-developmental dentinogenesis.
Topics: Animals; Carrier Proteins; Dentin; Dentinogenesis; Extracellular Matrix Proteins; Mice; Phosphoproteins; Sialoglycoproteins
PubMed: 31862386
DOI: 10.1016/j.job.2019.11.001 -
Current Genomics Apr 2018During the last decades, a large amount of newly described microduplications and microdeletions associated with intellectual disability (ID) and related neuropsychiatric... (Review)
Review
During the last decades, a large amount of newly described microduplications and microdeletions associated with intellectual disability (ID) and related neuropsychiatric diseases have been discovered. However, due to natural limitations, a significant part of them has not been the focus of multidisciplinary approaches. Here, we address previously undescribed chromosome 4q21.2q21.3 microduplication for gene prioritization, evaluation of cognitive abilities and estimation of genomic mechanisms for brain dysfunction by molecular cytogenetic (cytogenomic) and gene expression (meta-) analyses as well as for neuropsychological assessment. We showed that duplication at 4q21.2q21.3 is associated with moderate ID, cognitive deficits, developmental delay, language impairment, memory and attention problems, facial dysmorphisms, congenital heart defect and dentinogenesis imperfecta. Gene-expression meta-analysis prioritized the following genes: ENOPH1, AFF1, DSPP, SPARCL1, and SPP1. Furthermore, genotype/phenotype correlations allowed the attribution of each gene gain to each phenotypic feature. Neuropsychological testing showed visual-perceptual and fine motor skill deficits, reduced attention span, deficits of the nominative function and problems in processing both visual and aural information. Finally, emerging approaches including molecular cytogenetic, bioinformatic (genome/epigenome meta-analysis) and neuropsychological methods are concluded to be required for comprehensive neurological, genetic and neuropsychological descriptions of new genomic rearrangements/diseases associated with ID.
PubMed: 29606904
DOI: 10.2174/1389202918666170717161426 -
Journal of Veterinary Dentistry Oct 2023Dentinogenesis imperfecta is a rare, autosomal dominant, hereditary disorder that occurs in humans and animals. In humans, known causative genetic mutations have been... (Review)
Review
Dentinogenesis imperfecta is a rare, autosomal dominant, hereditary disorder that occurs in humans and animals. In humans, known causative genetic mutations have been elucidated; however, veterinary literature on the topic is limited. This case report describes a 1-year-old female Labrador Retriever who presented for evaluation of generalized discoloration of the permanent dentition with historical discoloration of the deciduous dentition. Radiographic and histopathological findings will be discussed, as well as an in-depth review of the current human and veterinary literature pertaining to the pathogenesis and treatment options for dentinogenesis imperfecta.
PubMed: 37872656
DOI: 10.1177/08987564231208359 -
Orphanet Journal of Rare Diseases Aug 2018Dentinogenesis imperfecta (DGI) is a heritable disorder of dentin. Genetic analyses have found two subgroups in this disorder: DGI type I, a syndromic form associated...
BACKGROUND
Dentinogenesis imperfecta (DGI) is a heritable disorder of dentin. Genetic analyses have found two subgroups in this disorder: DGI type I, a syndromic form associated with osteogenesis imperfecta (OI), and DGI type II, a non-syndromic form. The differential diagnosis between types I and II is often challenging. Thus, the present cross-sectional study had two aims: to (i) investigate the prevalence and incidence of DGI type II among Swedish children and adolescents and (ii) search out undiagnosed cases of DGI type I by documenting the prevalence of clinical symptoms of OI in these individuals. We invited all public and private specialist pediatric dental clinics (n = 47) in 21 counties of Sweden to participate in the study. We then continuously followed up all reported cases during 2014-2017 in order to identify all children and adolescents presenting with DGI type II. Using a structured questionnaire and an examination protocol, pediatric dentists interviewed and examined patients regarding medical aspects such as bruising, prolonged bleeding, spraining, fractures, hearing impairment, and family history of osteoporosis and OI. Joint hypermobility and sclerae were assessed. The clinical oral examination, which included a radiographic examination when indicated, emphasized dental variables associated with OI.
RESULTS
The prevalence of DGI type II was estimated to be 0.0022% (95% CI, 0.0016-0.0029%) or 1 in 45,455 individuals. Dental agenesis occurred in 9% of our group. Other findings included tooth retention (17%), pulpal obliteration (100%), and generalized joint hypermobility (30%). Clinical and radiographic findings raised a suspicion of undiagnosed OI in one individual, a 2-year-old boy; he was later diagnosed with OI type IV.
CONCLUSIONS
These results show a significantly lower prevalence of DGI type II than previously reported and point to the importance of excluding OI in children with DGI.
Topics: Adolescent; Adult; Child; Child, Preschool; Connective Tissue; Cross-Sectional Studies; Dentin Dysplasia; Dentinogenesis Imperfecta; Extracellular Matrix Proteins; Female; Genetic Diseases, Inborn; Humans; Incidence; Infant; Male; Osteogenesis Imperfecta; Phosphoproteins; Sialoglycoproteins; Surveys and Questionnaires; Sweden; Young Adult
PubMed: 30134932
DOI: 10.1186/s13023-018-0887-2 -
Journal of Dentistry Jun 2021A better understanding of the microstructure and mechanical properties of enamel and dentine may enable practitioners to apply the current adhesive dentistry protocols... (Review)
Review
OBJECTIVES
A better understanding of the microstructure and mechanical properties of enamel and dentine may enable practitioners to apply the current adhesive dentistry protocols to clinical cases involving dentine disorders (dentinogenesis imperfecta or dentine dysplasia).
DATA/SOURCES
Publications (up to June 2020) investigating the microstructure of dentine disorders were browsed in a systematic search using the PubMed/Medline, Embase and Cochrane Library electronic databases. Two authors independently selected the studies, extracted the data in accordance with the PRISMA statement, and assessed the risk of bias with the Critical Appraisal Checklist. A Mann-Whitney U test was computed to compare tissues damage related to the two dentine disorders of interest.
STUDY SELECTION
From an initial total of 642 studies, only 37 (n = 164 teeth) were included in the present analysis, among which 18 investigating enamel (n = 70 teeth), 15 the dentine-enamel junction (n = 62 teeth), and 35 dentine (n = 156 teeth). Dentine is damaged in cases of dentinogenesis imperfecta and osteogenesis imperfecta (p = 2.55E-21 and p = 3.99E-21, respectively). These studies highlight a reduction in mineral density, hardness, modulus of elasticity and abnormal microstructure in dentine disorders. The majority of studies report an altered dentine-enamel junction in dentinogenesis imperfecta and in osteogenesis imperfecta (p = 6.26E-09 and p = 0.001, respectively). Interestingly, enamel is also affected in cases of dentinogenesis imperfecta (p = 0.0013), unlike to osteogenesis imperfecta (p = 0.056).
CONCLUSIONS
Taking into account all these observations, only a few clinical principles may be favoured in the case of adhesive cementation: (i) to preserve the residual enamel to enhance bonding, (ii) to sandblast the tooth surfaces to increase roughness, (iii) to choose a universal adhesive and reinforce enamel and dentine by means of infiltrant resins. As these recommendations are mostly based on in vitro studies, future in vivo studies should be conducted to confirm these hypotheses.
Topics: Dental Cements; Dental Enamel; Dentin; Hardness; Tooth
PubMed: 33798638
DOI: 10.1016/j.jdent.2021.103654 -
The Journal of Clinical Pediatric... 2019Dentinogenesis Imperfecta type II (DI2), also known as hereditary opalescent dentin, is one of the most common genetic disorders affecting the structure of dentin, not... (Review)
Review
Dentinogenesis Imperfecta type II (DI2), also known as hereditary opalescent dentin, is one of the most common genetic disorders affecting the structure of dentin, not related with osteogenesis imperfecta, which involves both primary and permanent dentitions. The purpose of this article is to perform a scoping review of the published peer-reviewed literature (1986-2017) on DI2 management in children and to outline the most relevant clinical findings extracted from this review. Forty four articles were included in the present scoping review. According to the extracted data, the following are the most important tasks to be performed in clinical pediatric dentistry: to re-establish the oral mastication, esthetics, and speech, and the development of vertical growth of alveolar bone and facial muscles; to reduce the tendency to develop caries, periapical lesions and pain; to preserve vitality, form, and size of the dentition; to avoid interfering with the eruption process of permanent teeth; to decrease the risk of tooth fractures and occlusion disturbances; to return the facial profile to a more normal appearance; and to prevent or treat possible temporomandibular joint problems. Therefore, Pediatric Dentists should bear in mind that early diagnosis and treatment, together a long-term follow-up of DI2 in children, continue to be the best approaches for achieving enhanced patient psychological well-being and, in consequence, their quality of life.
Topics: Child; Child, Preschool; Dental Care for Children; Dentinogenesis Imperfecta; Dentition, Permanent; Esthetics, Dental; Humans; Quality of Life
PubMed: 30964718
DOI: 10.17796/1053-4625-43.3.1 -
Monographs in Oral Science 2023The development of the human dentition is prone to disruption due to its delicate and complex nature - including variations in tooth number and anatomical form and in... (Review)
Review
The development of the human dentition is prone to disruption due to its delicate and complex nature - including variations in tooth number and anatomical form and in the characteristics of enamel, dentine, and cementum. This chapter will focus on developmental defects of dental enamel (DDE) and dentine (DDD), which can be associated with considerable treatment burden on an individual, often related to the change in dental hard tissue characteristics in those at increased caries risk. DDE are prevalent and can be related to genetic conditions such as amelogenesis imperfecta and environmental challenges such as direct physical trauma to the developing tooth or systemic insults during the different phases of amelogenesis. Phenotypical variability can be great, making diagnosis difficult in many cases. There are two major enamel defects - the quantitative defect of hypoplasia and the qualitative defect of hypomineralization. DDDs are less prevalent than DDEs, with two major DDD types: dentinogenesis imperfecta and dentine dysplasia. The main features of the DDDs are enamel fracture exposing the dentine and subsequent wear, with enlarged pulp spaces in some variants. The appearance may be affected, with bulbous teeth and grey-blue to brown opalescent colouring. With respect to dental caries, developmental defects of the teeth, in themselves, do not cause caries risk; however, they can change the manifestation of the disease due to creating niches for biofilm accumulation and thereby increasing cleaning difficulty and changing the physical and chemical characteristics of dental hard tissues and how they react to cariogenic challenges.
Topics: Humans; Dental Caries; Dental Caries Susceptibility; Amelogenesis Imperfecta; Dental Enamel; Dentin
PubMed: 37364549
DOI: 10.1159/000530556 -
Current Osteoporosis Reports Feb 2016Osteogenesis imperfecta (OI) is a rare disorder of type 1 collagen with 13 currently identified types attributable to inherited abnormalities in type 1 collagen amount,... (Review)
Review
Osteogenesis imperfecta (OI) is a rare disorder of type 1 collagen with 13 currently identified types attributable to inherited abnormalities in type 1 collagen amount, structure, or processing. The disease is characterized by an increased susceptibility to bony fracture. In addition to the skeletal phenotype, common additional extraskeletal manifestations include blue sclerae, dentinogenesis imperfecta, vascular fragility, and hearing loss. Medical management is focused on minimizing the morbidity of fractures, pain, and bone deformities by maximizing bone health. Along with optimizing Vitamin D status and calcium intake and physical/occupational therapy, individualized surgical treatment may be indicated. Pharmacological therapy with bisphosphonate medications is now routinely utilized for moderate to severe forms and appears to have a good safety profile and bone health benefits. New therapies with other anti-resorptives as well as anabolic agents and transforming growth factor (TGF)β antibodies are in development. Other potential treatment modalities could include gene therapy or mesenchymal cell transplant. In the future, treatment choices will be further individualized in order to reduce disease morbidity and mortality.
Topics: Bone Density Conservation Agents; Calcium; Diphosphonates; Fractures, Spontaneous; Humans; Occupational Therapy; Osteogenesis Imperfecta; Physical Therapy Modalities; Resistance Training; Vitamin D
PubMed: 26861807
DOI: 10.1007/s11914-016-0299-y -
Clinical Oral Investigations Apr 2024Dentinogenesis imperfecta (DI) is an inherited dentin defect and may be isolated or associated with disorders such as osteogenesis imperfecta, odontochondrodysplasia...
OBJECTIVE
Dentinogenesis imperfecta (DI) is an inherited dentin defect and may be isolated or associated with disorders such as osteogenesis imperfecta, odontochondrodysplasia Ehler-Danlos and others. Isolated DI is caused mainly by pathogenic variants in DSPP gene and around 50 different variants have been described in this gene. Herein, we report on 19 patients from two unrelated Egyptian families with isolated DI. Additionally, we focused on genetic counselling of the two families.
MATERIALS AND METHODS
The patients were examined clinically and dentally. Panoramic X-rays were done to some patients. Whole exome sequencing (WES) and Sanger sequencing were used.
RESULTS
WES revealed two new nonsense variants in DSPP gene, c.288T > A (p.Tyr96Ter) and c.255G > A (p.Trp85Ter). Segregation analysis by Sanger sequencing confirmed the presence of the first variant in all affected members of Family 1 while the second variant was confirmed to be de novo in the patient of Family 2.
CONCLUSIONS AND CLINICAL RELEVANCE
Our study extends the number of DSPP pathogenic variants and strengthens the fact that DSPP is the most common DI causative gene irrespective of patients' ethnicity. In addition, we provide insights on genetic counseling issues in patients with inherited DSPP variants taking into consideration the variable religion, culture and laws in our society.
Topics: Humans; Dentinogenesis Imperfecta; Genetic Counseling; Ethnicity; Osteochondrodysplasias; Radiography, Panoramic
PubMed: 38630328
DOI: 10.1007/s00784-024-05636-z -
Oral Diseases Mar 2019Hereditary dentin disorders include dentinogenesis imperfecta (DGI) and dentin dysplasia (DD), which are autosomal dominant diseases characterized by altered dentin... (Review)
Review
Hereditary dentin disorders include dentinogenesis imperfecta (DGI) and dentin dysplasia (DD), which are autosomal dominant diseases characterized by altered dentin structure such as abnormality in dentin mineralization and the absence of root dentin. Shields classified DGI into three subgroups and DD into two subtypes. Although they are all hereditary dentin diseases, they do not share the same causative genes. To date, the pathogenic genes of DGI type I, which is considered a clinical manifestation of syndrome osteogenesis imperfecta, include COL1A1 and COL1A2. Mutations of the DSPP gene, which encodes the dentin sialophosphoprotein, a major non-collagenous protein, are responsible for three isolated dentinal diseases: DGI-II, DGI-III, and DD-II. However, DD-I appears to be special in that researchers have found three pathogenicity genes-VPS4B, SSUH2, and SMOC2-in three affected families from different countries. It is believed that DD-I is a genetically heterogeneous disease and is distinguished from other types of dentin disorders. This review summarizes the DD-I literature in the context of clinical appearances, radiographic characteristics, and functions of its pathogenic genes and aims to serve clinicians in further understanding and diagnosing this disease.
Topics: ATPases Associated with Diverse Cellular Activities; Caenorhabditis elegans Proteins; Calcium-Binding Proteins; Dentin Dysplasia; Dentinogenesis Imperfecta; Diagnosis, Differential; Endosomal Sorting Complexes Required for Transport; Genetic Heterogeneity; Humans; Phosphoprotein Phosphatases
PubMed: 29575674
DOI: 10.1111/odi.12861