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PeerJ 2018Osteogenesis imperfecta (OI) is a genetic disorder that is usually caused by disturbed production of collagen type I. Depending on its severity in the patient, this...
Osteogenesis imperfecta (OI) is a genetic disorder that is usually caused by disturbed production of collagen type I. Depending on its severity in the patient, this disorder may create difficulties and challenges for the dental practitioner. The goal of this article is to provide guidelines based on scientific evidence found in the current literature for practitioners who are or will be involved in the care of these patients. A prudent approach is recommended, as individuals affected by OI present with specific dentoalveolar problems that may prove very difficult to address. Recommended treatments for damaged/decayed teeth in the primary dentition are full-coverage restorations, including stainless steel crowns or zirconia crowns. Full-coverage restorations are also recommended in the permanent dentition. Intracoronal restorations should be avoided, as they promote structural tooth loss. Simple extractions can also be performed, but not immediately before or after intravenous bisphosphonate infusions. Clear aligners are a promising option for orthodontic treatment. In severe OI types, such as III or IV, orthognathic surgery is discouraged, despite the significant skeletal dysplasia present. Given the great variations in the severity of OI and the limited quantity of information available, the best treatment option relies heavily on the practitioner's preliminary examination and judgment. A multidisciplinary team approach is encouraged and favored in more severe cases, in order to optimize diagnosis and treatment.
PubMed: 30128210
DOI: 10.7717/peerj.5464 -
Frontiers in Genetics 2018Concerns over the cost and destructive nature of dental treatment have led to the call for novel minimally invasive, biologically based restorative solutions. For... (Review)
Review
Concerns over the cost and destructive nature of dental treatment have led to the call for novel minimally invasive, biologically based restorative solutions. For patients with toothache, this has resulted in a shift from invasive root-canal-treatment (RCT) toward more conservative vital-pulp-treatment (VPT) procedures, aimed to protect the pulp and harness its natural regenerative capacity. If the dental pulp is exposed, as long as the infection and inflammation can be controlled, conservative therapies can promote the formation of new tertiary dentine in a stem cell-led reparative process. Crucially, the volume and quality of new dentine is dependent on the material applied; however, currently available dental-materials are limited by non-specific action, cytotoxicity and poor clinical handling. Looking to the future, an improved understanding of the cellular regulators of pulpal inflammation and associated repair mechanisms is critical to predict pulpal responses and devise novel treatment strategies. Epigenetic modifications of DNA-associated proteins and the influences of non-coding RNAs have been demonstrated to control the self-renewal of stem cell populations as well as regulate mineralised tissue development and repair. Notably, the stability of microRNAs and their relative ease of sampling from pulpal blood highlight their potential for application as diagnostic inflammatory biomarkers, while increased understanding of their actions will not only enhance our knowledge of pulpal disease and repair, but also identify novel molecular targets. The potential therapeutic application of epigenetic modifying agents, DNA-methyltransferase-inhibitors (DNMTi) and histone-deacetylase-inhibitors (HDACi), have been shown to promote mineralisation and repair processes in dental-pulp-cell (DPC) populations as well as induce the release of bioactive dentine-matrix-components. Consequently, HDACis and DNMTis have the potential to enhance tertiary dentinogenesis by influencing the cellular and tissue processes at low concentrations with minimal side effects, providing an opportunity to develop a topically placed, inexpensive bio-inductive restorative material. The aim of this review is to highlight the potential role of epigenetic approaches in the treatment of the damaged dental pulp, considering the opportunities and obstacles, such as off-target effects, delivery mechanisms, for the therapeutic use of miRNA as an inflammatory biomarker or molecular target, before discussing the application of HDACi and DNMTi to the damaged pulp to stimulate repair.
PubMed: 30131827
DOI: 10.3389/fgene.2018.00311 -
Journal of Bone Metabolism Feb 2021The bone and dentin have distinct healing processes. The healing process of bones is regenerative, as newly formed tissues are morphologically and functionally similar...
The bone and dentin have distinct healing processes. The healing process of bones is regenerative, as newly formed tissues are morphologically and functionally similar to the original bone structures. In contrast, the healing process of dentin is reparative due to its failure to replicate some of its key morphological features. In this review, we compare and contrast the healing processes of bone and dentin. We describe how distinct morphological and physiological structures of the 2 tissues translate into different signaling molecules, growth factors, and matrix protein secretion.
PubMed: 33730779
DOI: 10.11005/jbm.2021.28.1.1 -
Journal of Dental Research Apr 2021Odontoblast differentiation is a complex and multistep process regulated by signaling pathways, including the Wnt/β-catenin signaling pathway. Both positive and...
Odontoblast differentiation is a complex and multistep process regulated by signaling pathways, including the Wnt/β-catenin signaling pathway. Both positive and negative effects of Wnt/β-catenin signaling on dentinogenesis have been reported, but the underlying mechanisms of these conflicting results are still unclear. To gain a better insight into the role of Wnt/β-catenin in dentinogenesis, we used dental pulp cells from a panel of transgenic mice, in which fluorescent protein expression identifies cells at different stages of odontoblast and osteoblast differentiation. Our results showed that exposure of pulp cells to WNT3a at various times and durations did not induce premature differentiation of odontoblasts. These treatments supported the survival of undifferentiated cells in dental pulp and promoted the formation of 2.3GFP preodontoblasts and their rapid transition into differentiated odontoblasts expressing DMP1-Cherry and DSPP-Cerulean transgenes. WNT3a also promoted osteogenesis in dental pulp cultures. These findings provide critical information for the development of improved treatments for vital pulp therapy and dentin regeneration.
Topics: Animals; Cell Differentiation; Dental Pulp; Dentinogenesis; Mice; Odontoblasts; Wnt Signaling Pathway; beta Catenin
PubMed: 33103548
DOI: 10.1177/0022034520967353 -
Progress in Biomaterials Dec 2018Infection of the dental pulp will result in inflammation and eventually tissue necrosis which is treated conventionally by pulpectomy and root canal treatment. Advances... (Review)
Review
Infection of the dental pulp will result in inflammation and eventually tissue necrosis which is treated conventionally by pulpectomy and root canal treatment. Advances in regenerative medicine and tissue engineering along with the introduction of new sources of stem cells have led to the possibility of pulp tissue regeneration. This systematic review analyzes animal studies published since 2010 to determine the ability of stem cell therapy to regenerate the dentine-pulp complex (DPC) and the success of clinical protocols. In vitro and human clinical studies are excluded and only the experimental studies on animal models were included. Dental pulp stem cells constitute the most commonly used cell type. The majority of stem cells are incorporated into various types of scaffold and implanted into root canals. Some of the studies combine growth factors with stem cells in an attempt to improve the outcome. Studies of ectopic transplantation using small animal models are simple and non-systematic evaluation techniques. Stem cell concentrations have not been so far reported; therefore, the translational value of such animal studies remains questionable. Though all types of stem cells appear capable of regenerating a dentine-pulp complex, still several factors have been considered in selecting the cell type. Co-administrative factors are essential for inducing the systemic migration of stem cells, and their vascularization and differentiation into odontoblast-like cells. Scaffolds provide a biodegradable structure able to control the release of growth factors. To identify problems and reduce costs, novel strategies should be initially tested in subcutaneous or renal capsule implantation followed by root canal models to confirm results.
PubMed: 30267369
DOI: 10.1007/s40204-018-0100-7 -
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 -
Biomolecules Jul 2021Intracellular Ca signaling engendered by Ca influx and mobilization in odontoblasts is critical for dentinogenesis induced by multiple stimuli at the dentin surface....
Intracellular Ca signaling engendered by Ca influx and mobilization in odontoblasts is critical for dentinogenesis induced by multiple stimuli at the dentin surface. Increased Ca is exported by the Na-Ca exchanger (NCX) and plasma membrane Ca-ATPase (PMCA) to maintain Ca homeostasis. We previously demonstrated a functional coupling between Ca extrusion by NCX and its influx through transient receptor potential channels in odontoblasts. Although the presence of PMCA in odontoblasts has been previously described, steady-state levels of mRNA-encoding PMCA subtypes, pharmacological properties, and other cellular functions remain unclear. Thus, we investigated PMCA mRNA levels and their contribution to mineralization under physiological conditions. We also examined the role of PMCA in the Ca extrusion pathway during hypotonic and alkaline stimulation-induced increases in intracellular free Ca concentration ([Ca]). We performed RT-PCR and mineralization assays in human odontoblasts. [Ca] was measured using fura-2 fluorescence measurements in odontoblasts isolated from newborn Wistar rat incisor teeth and human odontoblasts. We detected mRNA encoding PMCA1-4 in human odontoblasts. The application of hypotonic or alkaline solutions transiently increased [Ca] in odontoblasts in both rat and human odontoblasts. The Ca extrusion efficiency during the hypotonic or alkaline solution-induced [Ca] increase was decreased by PMCA inhibitors in both cell types. Alizarin red and von Kossa staining showed that PMCA inhibition suppressed mineralization. In addition, alkaline stimulation (not hypotonic stimulation) to human odontoblasts upregulated the mRNA levels of dentin matrix protein-1 (DMP-1) and dentin sialophosphoprotein (DSPP). The PMCA inhibitor did not affect DMP-1 or DSPP mRNA levels at pH 7.4-8.8 and under isotonic and hypotonic conditions, respectively. We also observed PMCA1 immunoreactivity using immunofluorescence analysis. These findings indicate that PMCA participates in maintaining [Ca] homeostasis in odontoblasts by Ca extrusion following [Ca] elevation. In addition, PMCA participates in dentinogenesis by transporting Ca to the mineralizing front (which is independent of non-collagenous dentin matrix protein secretion) under physiological and pathological conditions following mechanical stimulation by hydrodynamic force inside dentinal tubules, or direct alkaline stimulation by the application of high-pH dental materials.
Topics: Animals; Calcium; Cell Line; Dentin; Humans; Odontoblasts; Plasma Membrane Calcium-Transporting ATPases; Rats; Rats, Wistar; Tooth Calcification
PubMed: 34356633
DOI: 10.3390/biom11071010 -
European Journal of Medical Genetics Nov 2023Osteogenesis imperfecta (OI) and hypophosphatasia (HPP) are rare skeletal disorders caused by mutations in the genes encoding collagen type I (COL1A, COL1A2) and...
Combination of osteogenesis imperfecta and hypophosphatasia in three children with multiple fractures, low bone mass and severe osteomalacia, a challenge for therapeutic management.
Osteogenesis imperfecta (OI) and hypophosphatasia (HPP) are rare skeletal disorders caused by mutations in the genes encoding collagen type I (COL1A, COL1A2) and tissue-non-specific isoenzyme of alkaline phosphatase (ALPL), respectively. Both conditions result in skeletal deformities and bone fragility although bone tissue abnormalities differ considerably. Children with OI have low bone mass and hypermineralized matrix, whereas HPP children develop rickets and osteomalacia. We report a family, father and three children, affected with growth retardation, low bone mass and recurrent fractures. None of them had rickets, blue sclera or dentinogenesis imperfecta. ALP serum levels were low and genetics revealed in the four probands heterozygous pathogenic mutations in COL1A2 c.838G > A (p.Gly280Ser) and in ALPL c.1333T > C (p.Ser445Pro). After multidisciplinary meeting, a diagnostic transiliac bone biopsy was indicated for each sibling for therapeutic decision. Bone histology and histomorphometry, as compared to reference values of children with OI type I as well as, to a control pediatric patient harboring the same COL1A2 mutation, revealed similarly decreased trabecular bone volume, increased osteocyte lacunae, but additionally severe osteomalacia. Quantitative backscattered electron imaging demonstrated that bone matrix mineralization was not as decreased as expected for osteomalacia. In summary, we observed within each biopsy samples classical features of OI and classical features of HPP. The apparent nearly normal bone mineralization density distribution results presumably from divergent effects of OI and HPP on matrix mineralization. A combination therapy was initiated with ALP enzyme-replacement and one month later with bisphosphonates. The ongoing treatment led to improved skeletal growth, increased BMD and markedly reduced fracture incidence.
Topics: Child; Humans; Osteogenesis Imperfecta; Hypophosphatasia; Osteomalacia; Fractures, Multiple; Mutation; Alkaline Phosphatase; Calcinosis; Rickets
PubMed: 37758163
DOI: 10.1016/j.ejmg.2023.104856 -
BMC Oral Health Dec 2021Biocompatibility and induction of mineralized tissue formation are the properties expected from a material used in vital pulp therapy and repair of perforations. Cold...
Comparative evaluation of the effect of cold ceramic and MTA-Angelus on cell viability, attachment and differentiation of dental pulp stem cells and periodontal ligament fibroblasts: an in vitro study.
BACKGROUND
Biocompatibility and induction of mineralized tissue formation are the properties expected from a material used in vital pulp therapy and repair of perforations. Cold ceramic (SJM, Iran; CC) is a newly introduced calcium silicate-based cement for above mentioned therapeutic applications. This in-vitro study aimed to compare the effect of CC and White MTA-Angelus (MTA) on cell viability, attachment, odontogenic differentiation, and calcification potential of human dental pulp stem cells (DPSCs) and periodontal ligament fibroblasts (PDLFs).
METHODS
Cell viability of DPSCs and PDLFs was assessed using MTT on days 1, 3, 7, and 14 (n = 9) in contact with freshly mixed and set states of CC and MTA. Field emission scanning electron micrographs (FESEM) were taken to evaluate cell-bioceramic interaction (n = 6). Gene expression levels of osteo/odontogenic markers (Dentin sialophosphoprotein, Dentin matrix protein 1, Collagen type I alpha 1, and Alkaline phosphatase (DSPP, DMP1, COL 1A1, and ALP, respectively) (n = 8) were assessed using qrt-PCR. ALP enzymatic activity was evaluated to assess the mineralization potential. A two-way ANOVA test was applied, and p < 0.05 was considered to be statistically significant.
RESULTS
The effect of freshly mixed and set MTA and CC on the survival of DPSCs and PDLFs in all study groups was statistically similar and comparable to the positive control group (p > 0.05); the only exception was for the viability of PDLFs in contact with freshly mixed cements on day 1, showing a more significant cytotoxic effect compared to the control and the set state of materials (p < 0.05). PDLFs attached well on CC and MTA. The spread and pseudopodium formation of the cells increased on both samples from day 1 to day 14. Contact of MTA and CC with DPSCs similarly increased expression of all dentinogenesis markers studied on days 7 and 14 compared to the control group (p < 0.001), except for DSPP expression on day 7 (p = 0.46 and p = 0.99 for MTA and CC, respectively).
CONCLUSIONS
Within the limitation of this in-vitro study, cold ceramic and MTA-Angelus showed high biocompatibility and induced increased expression of osteo/dentinogenic markers. Therefore, cold ceramic can be a suitable material for vital pulp therapy and the repair of root perforations.
Topics: Aluminum Compounds; Bismuth; Calcium Compounds; Cell Differentiation; Cell Survival; Cells, Cultured; Ceramics; Dental Pulp; Drug Combinations; Fibroblasts; Humans; Oxides; Periodontal Ligament; Silicates; Stem Cells
PubMed: 34876089
DOI: 10.1186/s12903-021-01979-1 -
International Journal of Biomaterials 2021Introducing therapeutic ions into pulp capping materials has been considered a new approach for enhancing regeneration of dental tissues. However, no studies have been...
Introducing therapeutic ions into pulp capping materials has been considered a new approach for enhancing regeneration of dental tissues. However, no studies have been reported on its dentinogenic effects on human dental pulp cells (HDPCs). This study was designed to investigate the effects of magnesium (Mg) on cell attachment efficiency, proliferation, differentiation, and mineralization of HDPCs. HDPCs were cultured with 0.5 mM, 1 mM, 2 mM, 4 mM, and 8 mM concentrations of supplemental Mg and 0 mM (control). Cell attachment was measured at 4, 8, 12, 16, and 20 hours. Cell proliferation rate was evaluated at 3, 7, 10, 14, and 21 days. Crystal violet staining was used to determine cell attachment and proliferation rate. Alkaline phosphatase (ALP) activity was assessed using the fluorometric assay at 7, 10, and 14 days. Mineralization of cultures was measured by Alizarin red staining. Statistical analysis was done using multiway analysis of variance (multiway ANOVA) with Wilks' lambda test. Higher cell attachment was shown with 0.5 mM and 1 mM at 16 hours compared to control ( < 0.0001). Cells with 0.5 mM and 1 mM supplemental Mg showed significantly higher proliferation rates than control at 7, 10, 14, and 21 days ( < 0.0001). However, cell proliferation rates decreased significantly with 4 mM and 8 mM supplemental Mg at 14 and 21 days ( < 0.0001). Significantly higher levels of ALP activity and mineralization were observed in 0.5 mM, 1 mM, and 2 mM supplemental Mg at 10 and 14 days ( < 0.0001). However, 8 mM supplemental Mg showed lower ALP activity compared to control at 14 days ( < 0.0001), while 4 mM and 8 mM supplemental Mgshowed less mineralization compared to control ( < 0.0001). The study indicated that the optimal (0.5-2 mM) supplemental Mg concentrations significantly upregulated HDPCs by enhancing cell attachment, proliferation rate, ALP activity, and mineralization. Magnesium-containing biomaterials could be considered for a future novel dental pulp-capping additive in regenerative endodontics.
PubMed: 34840576
DOI: 10.1155/2021/6567455