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Journal of Dental Research May 2015
Review
Topics: Amelogenesis; Amino Acid Sequence; Animals; Conserved Sequence; Dental Enamel; Dental Enamel Proteins; Gene Duplication; Humans; Mice; Mice, Transgenic
PubMed: 25900605
DOI: 10.1177/0022034515572442 -
International Journal of Molecular... Feb 2021Amelogenesis imperfecta is a congenital form of enamel hypoplasia. Although a number of genetic mutations have been reported in humans, the regulatory network of these...
Amelogenesis imperfecta is a congenital form of enamel hypoplasia. Although a number of genetic mutations have been reported in humans, the regulatory network of these genes remains mostly unclear. To identify signatures of biological pathways in amelogenesis imperfecta, we conducted bioinformatic analyses on genes associated with the condition in humans. Through an extensive search of the main biomedical databases, we found 56 genes in which mutations and/or association/linkage were reported in individuals with amelogenesis imperfecta. These candidate genes were further grouped by function, pathway, protein-protein interaction, and tissue-specific expression patterns using various bioinformatic tools. The bioinformatic analyses highlighted a group of genes essential for extracellular matrix formation. Furthermore, advanced bioinformatic analyses for microRNAs (miRNAs), which are short non-coding RNAs that suppress target genes at the post-transcriptional level, predicted 37 candidates that may be involved in amelogenesis imperfecta. To validate the miRNA-gene regulation association, we analyzed the target gene expression of the top seven candidate miRNAs: miR-3195, miR-382-5p, miR-1306-5p, miR-4683, miR-6716-3p, miR-3914, and miR-3935. Among them, miR-1306-5p, miR-3195, and miR-3914 were confirmed to regulate ameloblast differentiation through the regulation of genes associated with amelogenesis imperfecta in AM-1 cells, a human ameloblastoma cell line. Taken together, our study suggests a potential role for miRNAs in amelogenesis imperfecta.
Topics: Ameloblasts; Amelogenesis Imperfecta; Cell Differentiation; Cell Line; Computational Biology; Humans; MicroRNAs; Protein Interaction Maps; Reproducibility of Results
PubMed: 33672174
DOI: 10.3390/ijms22042202 -
Journal of Prosthodontics : Official... Jul 2019The oral rehabilitation of adolescent patients with amelogenesis imperfecta (AI) is complex due to the presence of mixed dentition with altered eruption sequence. In... (Review)
Review
The oral rehabilitation of adolescent patients with amelogenesis imperfecta (AI) is complex due to the presence of mixed dentition with altered eruption sequence. In this article, the interdisciplinary treatment approach for adolescent patients with AI is discussed. The types and timing of treatments at various stages of growth are described through a literature review on this topic. AI is an inherited condition that disturbs the development of the enamel structure. Because of the presence of mixed dentition, definitive treatment options often have to be delayed until eruption of permanent dentition is complete, requiring careful treatment coordination and proper sequencing between different dental disciplines starting at a young age. Adolescent patients require prosthodontic treatment design that can be adapted to the changes in arch shapes, sizes, interarch relationship, and esthetic needs. AI patients are often challenged with both excessive and limited restorative spaces within the same arch due to the abnormal growth patterns, enamel structure, tooth size, and tooth shape. Therefore, careful determination of the required restorative space is critical to ensure optimal prognosis. This clinical report discusses treatment recommendations, timing of various treatment modalities, and involvement of appropriate interdisciplinary teams for managing adolescent patients.
Topics: Adolescent; Amelogenesis Imperfecta; Dental Enamel; Esthetics, Dental; Humans; Tooth; Tooth Eruption
PubMed: 31054208
DOI: 10.1111/jopr.13069 -
Scientific Reports Feb 2022As the hardest tissue in the human body, tooth enamel formation is a highly regulated process involving several stages of differentiation and key regulatory genes. One...
As the hardest tissue in the human body, tooth enamel formation is a highly regulated process involving several stages of differentiation and key regulatory genes. One such gene, tryptophan-aspartate repeat domain 72 (WDR72), has been found to cause a tooth enamel defect when deleted or mutated, resulting in a condition called amelogenesis imperfecta. Unlike the canonical genes regulating tooth development, WDR72 remains intracellularly and is not secreted to the enamel matrix space to regulate mineralization, and is found in other major organs of the body, namely the kidney, brain, liver, and heart. To date, a link between intracellular vesicle transport and enamel mineralization has been suggested, however identification of the mechanistic regulators has yet to be elucidated, in part due to the limitations associated with studying highly differentiated ameloblast cells. Here we show compelling evidence that WDR72 regulates endocytosis of proteins, both in vivo and in a novel in vitro ameloblast cell line. We elucidate WDR72's function to be independent of intracellular vesicle acidification while still leading to defective enamel matrix pH extracellularly. We identify a vesicle function associated with microtubule assembly and propose that WDR72 directs microtubule assembly necessary for membrane mobilization and subsequent vesicle transport. Understanding WDR72 function provides a mechanistic basis for determining physiologic and pathologic tissue mineralization.
Topics: Ameloblasts; Amelogenesis Imperfecta; Brain; Calcification, Physiologic; Cell Differentiation; Dental Enamel; Endocytosis; Humans; Kidney; Liver; Microtubules; Myocardium; Tooth
PubMed: 35181734
DOI: 10.1038/s41598-022-06751-1 -
Journal of Personalized Medicine Feb 2023Amelogenesis imperfecta (AI) is a heterogeneous collection of hereditary enamel defects. The affected enamel can be classified as hypoplastic, hypomaturation, or...
Amelogenesis imperfecta (AI) is a heterogeneous collection of hereditary enamel defects. The affected enamel can be classified as hypoplastic, hypomaturation, or hypocalcified in form. A better understanding of normal amelogenesis and improvements in our ability to diagnose AI through genetic testing can be realized through more complete knowledge of the genes and disease-causing variants that cause AI. In this study, mutational analysis was performed with whole exome sequencing (WES) to identify genetic etiology underlying the hypomaturation AI condition in affected families. Mutational analyses identified biallelic mutations in four hypomaturation AI families. Novel mutations include a homozygous deletion and insertion mutation (NM_182758.4: c.2680_2699delinsACTATAGTT, p.(Ser894Thrfs*15)), compound heterozygous mutations (paternal c.2332dupA, p.(Met778Asnfs*4)) and (maternal c.1287_1289del, p.(Ile430del)) and a homozygous 3694 bp deletion that includes exon 14 (NG_017034.2:g.96472_100165del). A homozygous recurrent mutation variant (c.1467_1468delAT, p.(Val491Aspfs*8)) was also identified. Current ideas on WDR72 structure and function are discussed. These cases expand the mutational spectrum of mutations causing hypomaturation AI and improve the possibility of genetic testing to accurately diagnose AI caused by defects.
PubMed: 36836560
DOI: 10.3390/jpm13020326 -
Operative Dentistry 2017Amelogenesis imperfecta (AI) refers to a group of rare genetic disorders that involve tooth development and that are passed down through families as a dominant trait....
Amelogenesis imperfecta (AI) refers to a group of rare genetic disorders that involve tooth development and that are passed down through families as a dominant trait. This condition is characterized by abnormal enamel formation caused by gene mutations that alter the quality and/or quantity of enamel. This dental problem can impact both primary and permanent dentition, varies among affected individuals, and results in esthetic and functional problems. This condition caused the patient in the current case report to have a lack of confidence when speaking. The treatment for amelogenesis imperfecta depends on the severity of the problem and age of the patient. It is crucial to plan a proper remedy, which requires collaboration among dental specialties to execute comprehensive dental treatment in order to provide a long-term solution with adequate esthetics. The current clinical study presents a patient affected by AI that was diagnosed when the patient was a child. The interdisciplinary treatment continued throughout his childhood and into adult life. The initial treatment consisted of resin composite veneers and stainless-steel crowns to restore the defective tooth structure. The malocclusion of the patient was corrected using a fixed orthodontic appliance that was placed when he had an entire permanent dentition. The treatment plan was eventually intended to include all ceramic crowns and veneers.
Topics: Amelogenesis Imperfecta; Child; Dental Veneers; Humans; Male; Malocclusion; Orthodontic Appliances; Overbite; Palatal Expansion Technique; Tooth Movement Techniques
PubMed: 28829932
DOI: 10.2341/13-256-S -
Frontiers in Physiology 2020Stromal interaction molecule 1 () is one of the main components of the store operated Ca entry (SOCE) signaling pathway. Individuals with mutated present severely...
BACKGROUND
Stromal interaction molecule 1 () is one of the main components of the store operated Ca entry (SOCE) signaling pathway. Individuals with mutated present severely hypomineralized enamel characterized as amelogenesis imperfecta (AI) but the downstream molecular mechanisms involved remain unclear. Circadian clock signaling plays a key role in regulating the enamel thickness and mineralization, but the effects of -mediated AI on circadian clock are unknown.
OBJECTIVES
The aim of this study is to examine the potential links between SOCE and the circadian clock during amelogenesis.
METHODS
We have generated mice with ameloblast-specific deletion of ( /Amelx-iCre, cKO) and analyzed circadian gene expression profile in compared to control ( /Amelx-iCre) using ameloblast micro-dissection and RNA micro-array of 84 circadian genes. Expression level changes were validated by qRT-PCR and immunohistochemistry.
RESULTS
deletion has resulted in significant upregulation of the core circadian activator gene Brain and Muscle Aryl Hydrocarbon Receptor Nuclear Translocation 1 () and downregulation of the circadian inhibitor Period 2 (). Our analyses also revealed that SOCE disruption results in dysregulation of two additional circadian regulators; p38α mitogen-activated protein kinase (MAPK14) and transforming growth factor-beta1 (TGF-β1). Both MAPK14 and TGF-β1 pathways are known to play major roles in enamel secretion and their dysregulation has been previously implicated in the development of AI phenotype.
CONCLUSION
These data indicate that disruption of SOCE significantly affects the ameloblasts molecular circadian clock, suggesting that alteration of the circadian clock may be partly involved in the development of -mediated AI.
PubMed: 32848861
DOI: 10.3389/fphys.2020.00920 -
International Journal of Paediatric... Nov 2022Amelogenesis imperfecta (AI) is an inherited disorder of enamel development that is challenging to treat and often associated with negative patient and parental...
BACKGROUND
Amelogenesis imperfecta (AI) is an inherited disorder of enamel development that is challenging to treat and often associated with negative patient and parental outcomes. Social media provides a valuable perspective on patients' and dental professionals' experience of AI and dental care.
AIM
To explore how the public and dental professionals use social media to discuss AI.
DESIGN
A cross-sectional study involving a systemic search of eight social media platforms using the search term 'amelogenesis imperfecta'. Relevant posts were selected using predefined eligibility criteria. Word content of eligible posts was qualitatively analysed using a thematic framework approach.
RESULTS
A total of 555 posts were identified, of which 144 were eligible for analysis. For dental professionals, the posts included case reports and seeking and sharing of information. For the public, the posts were related to individuals' experience of AI, dental treatment and outcome of treatment.
CONCLUSIONS
Posts from individuals affected by AI suggest a need for better distribution of reliable information and greater support. Case reports indicate that dental professionals find it challenging to recognise AI and determine appropriate treatment options. Social media could potentially be used to inform and support people with AI and allow dental professionals to share information and learning with peers.
Topics: Amelogenesis; Amelogenesis Imperfecta; Cross-Sectional Studies; Dentists; Humans; Social Media
PubMed: 35771161
DOI: 10.1111/ipd.13015 -
British Dental Journal Sep 2022Background Amelogenesis imperfecta (AI) can be challenging to manage due to the complexity and variation of presentation. Clear care pathways between general practice,...
Background Amelogenesis imperfecta (AI) can be challenging to manage due to the complexity and variation of presentation. Clear care pathways between general practice, specialist paediatric dentistry and adult services are required.Aim To assess the provision of specialist care and transitional care arrangements for paediatric patients with AI in the UK.Method An online survey was disseminated to members of the British Society of Paediatric Dentistry in January 2020. Descriptive analysis was used to interpret the quantitative and qualitative results.Results In total, 115 clinicians across all four nations participated. Most respondents (54%; n = 66), were based in the hospital dental service. Overall, 29% (n = 33) were consultants and 24% (n = 28) were specialists in paediatric dentistry. The most common patient age group seen was 6-12 years old. No clear AI referral pathway into specialist care was reported by 49% (n = 47). A clear transitional care pathway was deemed not to exist by 77% (n = 72), with 85.9% (n = 73) indicating a need. Qualitative analysis themes included 'unclear care pathways' and 'specialist care access problems'.Conclusion Access to specialist paediatric dental care and transition to adult services is not readily available throughout the UK for AI patients. There is a clear need to establish and improve existing pathways.
PubMed: 36171269
DOI: 10.1038/s41415-022-5077-x -
Frontiers in Physiology 2017During the secretory phase of their life-cycle, ameloblasts are highly specialized secretory cells whose role is to elaborate an extracellular matrix that ultimately... (Review)
Review
During the secretory phase of their life-cycle, ameloblasts are highly specialized secretory cells whose role is to elaborate an extracellular matrix that ultimately confers both form and function to dental enamel, the most highly mineralized of all mammalian tissues. In common with many other "professional" secretory cells, ameloblasts employ the unfolded protein response (UPR) to help them cope with the large secretory cargo of extracellular matrix proteins transiting their ER (endoplasmic reticulum)/Golgi complex and so minimize ER stress. However, the UPR is a double-edged sword, and, in cases where ER stress is severe and prolonged, the UPR switches from pro-survival to pro-apoptotic mode. The purpose of this review is to consider the role of the ameloblast UPR in the biology and pathology of amelogenesis; specifically in respect of amelogenesis imperfecta (AI) and fluorosis. Some forms of AI appear to correspond to classic proteopathies, where pathological intra-cellular accumulations of protein tip the UPR toward apoptosis. Fluorosis also involves the UPR and, while not of itself a classic proteopathic disease, shares some common elements through the involvement of the UPR. The possibility of therapeutic intervention by pharmacological modulation of the UPR in AI and fluorosis is also discussed.
PubMed: 28951722
DOI: 10.3389/fphys.2017.00653