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Der Orthopade Aug 2014Osteogenesis imperfecta (OI) is the most common genetic disease of bone and is characterized by fragile bones and growth disorders of varying severity. Most cases of OI...
BACKGROUND
Osteogenesis imperfecta (OI) is the most common genetic disease of bone and is characterized by fragile bones and growth disorders of varying severity. Most cases of OI are inherited autosomal dominant and caused by a mutation in the collagen type I gene.
DIAGNOSTICS
Indications for OI are bone fragility, stunted growth, scoliosis, skull deformities, blue sclera, loss of hearing, dentinogenesis imperfecta and increased laxity of ligaments and skin. In most cases it is possible to make a clinical diagnosis but a skin biopsy or genetic testing can be useful; however, negative results for these tests do not exclude OI.
THERAPY
Therapy must be carried out in a multidisciplinary team and includes conservative (e.g. physiotherapy, rehabilitation programs and orthopedic aids), operative (e.g. intramedullary stabilization procedures) and pharmaceutical (e.g. biphosphonates and growth hormones) procedures.
PROGNOSIS
The prognosis depends on the type of OI and ranges from normal life expectations for type 1 patients up to up to perinatal mortality for type II patients.
Topics: Adolescent; Bone Density Conservation Agents; Child; Child, Preschool; Combined Modality Therapy; Female; Fracture Fixation, Intramedullary; Humans; Infant; Infant, Newborn; Male; Osteogenesis Imperfecta; Physical Examination; Physical Therapy Modalities; Tomography, X-Ray Computed
PubMed: 25116245
DOI: 10.1007/s00132-013-2229-3 -
Oral Diseases Sep 2023This review aimed to summarize recent progress on syndromic dentin defects, promoting a better understanding of systemic diseases with dentin malformations, the... (Review)
Review
OBJECTIVE
This review aimed to summarize recent progress on syndromic dentin defects, promoting a better understanding of systemic diseases with dentin malformations, the molecules involved, and related mechanisms.
SUBJECTS AND METHODS
References on genetic diseases with dentin malformations were obtained from various sources, including PubMed, OMIM, NCBI, and other websites. The clinical phenotypes and genetic backgrounds of these diseases were then summarized, analyzed, and compared.
RESULTS
Over 10 systemic diseases, including osteogenesis imperfecta, hypophosphatemic rickets, vitamin D-dependent rickets, familial tumoral calcinosis, Ehlers-Danlos syndrome, Schimke immuno-osseous dysplasia, hypophosphatasia, Elsahy-Waters syndrome, Singleton-Merten syndrome, odontochondrodysplasia, and microcephalic osteodysplastic primordial dwarfism type II were examined. Most of these are bone disorders, and their pathogenic genes may regulate both dentin and bone development, involving extracellular matrix, cell differentiation, and metabolism of calcium, phosphorus, and vitamin D. The phenotypes of these syndromic dentin defects various with the involved genes, part of them are similar to dentinogenesis imperfecta or dentin dysplasia, while others only present one or two types of dentin abnormalities such as discoloration, irregular enlarged or obliterated pulp and canal, or root malformation.
CONCLUSION
Some specific dentin defects associated with systemic diseases may serve as important phenotypes for dentists to diagnose. Furthermore, mechanistic studies on syndromic dentin defects may provide valuable insights into isolated dentin defects and general dentin development or mineralization.
Topics: Humans; Dentinogenesis Imperfecta; Odontodysplasia; Osteogenesis Imperfecta; Dentin; Vitamin D
PubMed: 37094075
DOI: 10.1111/odi.14589 -
Current Oral Health Reports 2018Current dental treatments are based on conservative approaches, using inorganic materials and appliances.This report explores and discusses the newest achievements in... (Review)
Review
PURPOSE OF REVIEW
Current dental treatments are based on conservative approaches, using inorganic materials and appliances.This report explores and discusses the newest achievements in the field of "regenerative dentistry," based on the concept of biological repair as an alternative to the current conservative approach.
RECENT FINDINGS
The review covers and critically analyzes three main approaches of tooth repair: the re-mineralization of the enamel, the biological repair of dentin, and whole tooth engineering.
SUMMARY
The development of a concept of biological repair based on the role of the Wnt signaling pathway in reparative dentin formation offers a new translational approach into development of future clinical dental treatments.In the field of bio-tooth engineering, the current focus of the researchers remains the establishment of odontogenic cell-sources that would be viable and easily accessible for future bio-tooth engineering.
PubMed: 30524931
DOI: 10.1007/s40496-018-0196-9 -
Clinical Oral Implants Research Mar 2015Although regenerative treatment options are available, periodontal regeneration is still regarded as insufficient and unpredictable. (Review)
Review
BACKGROUND
Although regenerative treatment options are available, periodontal regeneration is still regarded as insufficient and unpredictable.
AIM
This review article provides scientific background information on the animated 3D film Cell-to-Cell Communication - Periodontal Regeneration.
RESULTS
Periodontal regeneration is understood as a recapitulation of embryonic mechanisms. Therefore, a thorough understanding of cellular and molecular mechanisms regulating normal tooth root development is imperative to improve existing and develop new periodontal regenerative therapies. However, compared to tooth crown and earlier stages of tooth development, much less is known about the development of the tooth root. The formation of root cementum is considered the critical element in periodontal regeneration. Therefore, much research in recent years has focused on the origin and differentiation of cementoblasts. Evidence is accumulating that the Hertwig's epithelial root sheath (HERS) has a pivotal role in root formation and cementogenesis. Traditionally, ectomesenchymal cells in the dental follicle were thought to differentiate into cementoblasts. According to an alternative theory, however, cementoblasts originate from the HERS. What happens when the periodontal attachment system is traumatically compromised? Minor mechanical insults to the periodontium may spontaneously heal, and the tissues can structurally and functionally be restored. But what happens to the periodontium in case of periodontitis, an infectious disease, after periodontal treatment? A non-regenerative treatment of periodontitis normally results in periodontal repair (i.e., the formation of a long junctional epithelium) rather than regeneration. Thus, a regenerative treatment is indicated to restore the original architecture and function of the periodontium. Guided tissue regeneration or enamel matrix proteins are such regenerative therapies, but further improvement is required. As remnants of HERS persist as epithelial cell rests of Malassez in the periodontal ligament, these epithelial cells are regarded as a stem cell niche that can give rise to new cementoblasts. Enamel matrix proteins and members of the transforming growth factor beta (TGF-ß) superfamily have been implicated in cementoblast differentiation.
CONCLUSION
A better knowledge of cell-to-cell communication leading to cementoblast differentiation may be used to develop improved regenerative therapies to reconstitute periodontal tissues that were lost due to periodontitis.
Topics: Cell Communication; Cementogenesis; Dentinogenesis; Guided Tissue Regeneration, Periodontal; Humans; Odontogenesis; Periodontal Ligament; Periodontitis; Tooth Movement Techniques
PubMed: 25639287
DOI: 10.1111/clr.12543 -
British Dental Journal Sep 2022This paper examines the various contemporary clinical interfaces between paediatric dentistry and restorative dentistry for patients with both acquired and congenital...
This paper examines the various contemporary clinical interfaces between paediatric dentistry and restorative dentistry for patients with both acquired and congenital abnormalities presenting to primary and secondary care. Dental trauma of the child or adolescent has long-standing implications on future oral health due to conditions such as ankylosis, pulp necrosis, coronal tissue loss or tooth loss, all of which provide significant challenges into adulthood. Similarly, congenital conditions, such as hypodontia and structural deficiencies or malformations, such as amelogenesis and dentinogenesis imperfecta, result in the need for collaborative, multi-speciality decision-making from a young age, creating a pathway for longitudinal multi-disciplinary team treatment planning.
Topics: Adolescent; Adult; Amelogenesis Imperfecta; Anodontia; Child; Humans; Oral Health; Patient Care Planning; Pediatric Dentistry
PubMed: 36151172
DOI: 10.1038/s41415-022-4983-2 -
Organogenesis Dec 2022The development and repair of dentin are strictly regulated by hundreds of genes. Abnormal dentin development is directly caused by gene mutations and dysregulation....
The development and repair of dentin are strictly regulated by hundreds of genes. Abnormal dentin development is directly caused by gene mutations and dysregulation. Understanding and mastering this signal network is of great significance to the study of tooth development, tissue regeneration, aging, and repair and the treatment of dental diseases. It is necessary to understand the formation and repair mechanism of dentin in order to better treat the dentin lesions caused by various abnormal properties, whether it is to explore the reasons for the formation of dentin defects or to develop clinical drugs to strengthen the method of repairing dentin. Molecular biology of genes related to dentin development and repair are the most important basis for future research.
Topics: Dentin; Dentinogenesis; Odontoblasts; Odontogenesis
PubMed: 35023442
DOI: 10.1080/15476278.2021.2022373 -
Wiener Medizinische Wochenschrift (1946) Jul 2015Osteogenesis imperfecta is a rare hereditary disease mostly caused by mutations impairing collagen synthesis and modification. Recently recessive forms have been... (Review)
Review
Osteogenesis imperfecta is a rare hereditary disease mostly caused by mutations impairing collagen synthesis and modification. Recently recessive forms have been described influencing differentiation and activity of osteoblasts and osteoclasts. Most prominent signs are fractures due to low traumata and deformities of long bones and vertebrae. Additional patients can be affected by dwarfism, scoliosis Dentinogenesis imperfecta, deafness and a blueish discoloration of the sclera. During childhood state of the art medical treatment are i.v. bisphosphonates to increase bone mass and to reduce fracture rate. Surgical interventions are needed to treat fractures, to correct deformities and should always be accompanied by physiotherapeutic and rehabilitative interventions.
Topics: Collagen Type I; Collagen Type I, alpha 1 Chain; Combined Modality Therapy; DNA Mutational Analysis; Diphosphonates; Female; Fracture Fixation; Fractures, Spontaneous; Genetic Carrier Screening; Humans; Infant; Infant, Newborn; Infusions, Intravenous; Male; Osteoblasts; Osteoclasts; Osteogenesis Imperfecta; Physical Therapy Modalities
PubMed: 26055811
DOI: 10.1007/s10354-015-0361-x -
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 Dec 2022This review describes the clinical, radiographic and histologic characteristics of dentinogenesis imperfecta diagnosed in two unrelated young dogs without evidence of... (Review)
Review
This review describes the clinical, radiographic and histologic characteristics of dentinogenesis imperfecta diagnosed in two unrelated young dogs without evidence of concurrent osteogenesis imperfecta. The dentition was noted to have generalized coronal discoloration ranging from grey-blue to golden brown. Clinical pulp exposure, coronal wear and fractures were observed as was radiographic evidence of endodontic disease, thin dentin walls or dystrophic obliteration of the pulp canal. The enamel was severely affected by attrition and abrasion despite histologically normal areas; loss was most likely due to poor adherence or support by the underlying abnormal dentin. Histologically, permanent and deciduous teeth examined showed thin, amorphous dentin without organized dentin tubules and odontoblasts had dysplastic cell morphology. Primary dentin disorders, including dentinogenesis imperfecta and dentin dysplasia, have been extensively studied and genetically characterized in humans but infrequently reported in dogs. Treatment in human patients is aimed at early recognition and multi-disciplinary intervention to restore and maintain normal occlusion, aesthetics, mastication and speech. Treatment in both humans and canine patients is discussed as is the documented genetic heritability of primary dentin disorders in humans.
Topics: Humans; Dogs; Animals; Dentinogenesis Imperfecta; Esthetics, Dental; Odontoblasts; Osteogenesis Imperfecta; Dentin; Dog Diseases
PubMed: 36113440
DOI: 10.1177/08987564221123419 -
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