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Acta Bio-medica : Atenei Parmensis Dec 2023Congenital heart disease (CHD) is an abnormality in the structure or function of the cardio-circulatory system present at birth and the ventricular septal defect (VSD)...
Congenital heart disease (CHD) is an abnormality in the structure or function of the cardio-circulatory system present at birth and the ventricular septal defect (VSD) is the most common CHD in children. This study aimed to determine any differences in the histological structure of primary teeth between both healthy children and those children with ventricular septal defects in Erbil City. Methods enrolled children were divided into two groups. Group I (control) & group II (CHD) aged between 6-10 years old. A total of 44 children were collected, (22 children) in each group. Enamel, dentin, and odontoblast layers were examined histologically. Unpaired t-test used for statistical analysis. Results: The histopathological sections showed a significant difference in enamel, dentin, and odontoblast layer thickness (255.8 ± 41.68- 406.4 ±46.39), (1156 ± 116.0 - 1320 ± 117.4) and (29.74 ± 7.66 -41.38 ± 12.06) respectively, with p values (P < 0.0001) for enamel and dentin layer, and P < 0.0004 for odontoblast layer. A study of the images in the CHD group showed that the tooth tissue lost its integrity and cohesion in some places, and the thickness of the enamel and dentin layer in this group was significantly reduced compared to group I. Tissue loss in enamel, pulp, and dentin cell were observed. Also, connective tissue layers in the pulp were disrupted. Conclusions: CHD can alter the natural structure formation of primary teeth. Histologically, enamel, dentin, and odontoblasts layer thickness reduction are found in primary teeth in children with ventricular septal defects.
Topics: Infant, Newborn; Humans; Child; Dentin; Odontoblasts; Heart Defects, Congenital; Tooth, Deciduous; Heart Septal Defects, Ventricular
PubMed: 38054687
DOI: 10.23750/abm.v94i6.14567 -
Developmental Biology Aug 2010Tricho-dento-osseous (TDO) syndrome is an autosomal dominant disorder characterized by abnormalities in the thickness and density of bones and teeth. A 4-bp deletion...
Tricho-dento-osseous (TDO) syndrome is an autosomal dominant disorder characterized by abnormalities in the thickness and density of bones and teeth. A 4-bp deletion mutation in the Distal-Less 3 (DLX3) gene is etiologic for most cases of TDO. To investigate the in vivo role of mutant DLX3 (MT-DLX3) on dentin development, we generated transgenic (TG) mice expressing MT-DLX3 driven by a mouse 2.3 Col1A1 promoter. Dentin defects were radiographically evident in all teeth and the size of the nonmineralized pulp was enlarged in TG mice, consistent with clinical characteristics in patients with TDO. High-resolution radiography, microcomputed tomography, and SEM revealed a reduced zone of mineralized dentin with anomalies in the number and organization of dentinal tubules in MT-DLX3 TG mice. Histological and immunohistochemical studies demonstrated that the decreased dentin was accompanied by altered odontoblast cytology that included disruption of odontoblast polarization and reduced numbers of odontoblasts. TUNEL assays indicated enhanced odontoblast apoptosis. Expression levels of the apoptotic marker caspase-3 were increased in odontoblasts in TG mice as well as in odontoblastic-like MDPC-23 cells transfected with MT-DLX3 cDNA. Expression of Runx2, Wnt 10A, and TBC1D19 colocalized with DLX3 expression in odontoblasts, and MT-DLX3 significantly reduced expression of all three genes. TBC1D19 functions in cell polarity and decreased TBC1D19 expression may contribute to the observed disruption of odontoblast polarity and apoptosis. These data indicate that MT-DLX3 acts to disrupt odontoblast cytodifferentiation leading to odontoblast apoptosis, and aberrations of dentin tubule formation and dentin matrix production, resulting in decreased dentin and taurodontism. In summary, this TG model demonstrates that MT-DLX3 has differential effects on matrix production and mineralization in dentin and bone and provides a novel tool for the investigation of odontoblast biology.
Topics: Animals; Bone and Bones; Caspase 3; Dentin; Ectodermal Dysplasia; Humans; Male; Mice; Mice, Transgenic; Odontoblasts; Odontogenesis; Sequence Deletion; Tooth
PubMed: 20510228
DOI: 10.1016/j.ydbio.2010.05.499 -
Anatomical Record (Hoboken, N.J. : 2007) Aug 2021Odontoblast processes are thin cytoplasmic projections that extend from the cell body at the periphery of the pulp toward the dentin-enamel junction. The odontoblast...
Odontoblast processes are thin cytoplasmic projections that extend from the cell body at the periphery of the pulp toward the dentin-enamel junction. The odontoblast processes function in the secretion, assembly and mineralization of dentin during development, participate in mechanosensation, and aid in dentin repair in mature teeth. Because they are small and densely arranged, their three-dimensional organization is not well documented. To gain further insight into how odontoblast processes contribute to odontogenesis, we used serial section electron microscopy and three-dimensional reconstructions to examine these processes in the predentin region of mouse molars and incisors. In molars, the odontoblast processes are tubular with a diameter of ~1.8 μm. The odontoblast processes near the incisor tip are similarly shaped, but those midway between the tip and apex are shaped like plates. The plates are radially aligned and longitudinally oriented with respect to the growth axis of the incisor. The thickness of the plates is approximately the same as the diameter of molar odontoblast processes. The plates have an irregular edge; the average ratio of width (midway in the predentin) to thickness is 2.3 on the labial side and 3.6 on the lingual side. The plate geometry seems likely to be related to the continuous growth of the incisor and may provide a clue as to the mechanisms by which the odontoblast processes are involved in tooth development.
Topics: Animals; Dentinogenesis; Incisor; Mice; Odontoblasts; Odontogenesis
PubMed: 33190419
DOI: 10.1002/ar.24570 -
Cellular and Molecular Life Sciences :... Jan 2003The amelogenins, the major proteins of the developing tooth enamel matrix, are highly conserved throughout most species studied. The gene structure is similar, with a... (Review)
Review
The amelogenins, the major proteins of the developing tooth enamel matrix, are highly conserved throughout most species studied. The gene structure is similar, with a set of seven exons and intervening introns, and remarkable conservation of particular exon sizes over divergent species. Studies of exon skipping and consequent alternative gene splicing suggest that, in vertebrates, exon definition is crucial. In this mechanism, exon size is important. If too small, an exon can be readily skipped, if too large, internal cryptic splice sites may be utilized. Other factors, such as intron length and specific nucleotide sequences at the splice boundaries also modulate splicing efficiency, but amelogenin gene splicing conforms well to the generalized exon length model. Exons 1, 2 and 7 are not subject to splicing that affects the secreted protein product, but exons 3, 4 and 5 are at the lower boundary of exon size, rendering them, 4 and 5 especially, subject to skipping. On the other hand, exon 6 is very long and has cryptic splicing sites that can be used. In the mouse, nine distinct splice product proteins have been detected. The question now is the functions of these products. The larger forms, those that contain the intact proline-rich, hydrophobic exon 6 domains, are important for enamel mineralization. Recent work suggests that the small proteins resulting from deletion of a major part of amelogenin gene exon 6 via utilization of a cryptic site may have signal transduction functions during tooth development. Furthermore, new work also suggests that odontoblasts transiently express the small amelogenins during the period that epithelial-mesenchymal signaling between preodontoblasts and preameloblasts determines the course of tooth development. The same peptides have been demonstrated to act on non-odontogenic cells and effect their phenotypic expression patterns in vitro, and to induce bone formation in implants in vivo.
Topics: Alternative Splicing; Ameloblasts; Amelogenin; Amino Acid Sequence; Animals; Base Sequence; Cattle; Cell Differentiation; Conserved Sequence; Dental Enamel Proteins; Exons; Humans; Mice; Odontoblasts; RNA, Messenger; Signal Transduction; Swine
PubMed: 12613657
DOI: 10.1007/s000180300003 -
International Journal of Oral Science Jan 2021Dental pulp can initiate its damage repair after an injury of the pulp-dentin complex by rearrangement of odontoblasts and formation of newly differentiated...
Dental pulp can initiate its damage repair after an injury of the pulp-dentin complex by rearrangement of odontoblasts and formation of newly differentiated odontoblast-like cells. Connexin 43 (Cx43) is one of the gap junction proteins that participates in multiple tissue repair processes. However, the role of Cx43 in the repair of the dental pulp remains unclear. This study aimed to determine the function of Cx43 in the odontoblast arrangement patterns and odontoblastic differentiation. Human teeth for in vitro experiments were acquired, and a pulp injury model in Sprague-Dawley rats was used for in vivo analysis. The odontoblast arrangement pattern and the expression of Cx43 and dentin sialophosphoprotein (DSPP) were assessed. To investigate the function of Cx43 in odontoblastic differentiation, we overexpressed or inhibited Cx43. The results indicated that polarized odontoblasts were arranged along the pulp-dentin interface and had high levels of Cx43 expression in the healthy teeth; however, the odontoblast arrangement pattern was slightly changed concomitant to an increase in the Cx43 expression in the carious teeth. Regularly arranged odontoblast-like cells had high levels of the Cx43 expression during the formation of mature dentin, but the odontoblast-like cells were not regularly arranged beneath immature osteodentin in the pulp injury models. Subsequent in vitro experiments demonstrated that Cx43 is upregulated during odontoblastic differentiation of the dental pulp cells, and inhibition or overexpression of Cx43 influence the odontoblastic differentiation. Thus, Cx43 may be involved in the maintenance of odontoblast arrangement patterns, and influence the pulp repair outcomes by the regulation of odontoblastic differentiation.
Topics: Animals; Cell Differentiation; Connexin 43; Dental Pulp; Extracellular Matrix Proteins; Odontoblasts; Phosphoproteins; Rats; Rats, Sprague-Dawley
PubMed: 33414369
DOI: 10.1038/s41368-020-00105-1 -
Journal of Dental Research Jul 2019Dentin sialophosphoprotein (DSPP) is an extracellular matrix protein highly expressed by odontoblasts in teeth. DSPP mutations in humans may cause dentinogenesis...
Dentin sialophosphoprotein (DSPP) is an extracellular matrix protein highly expressed by odontoblasts in teeth. DSPP mutations in humans may cause dentinogenesis imperfecta (DGI), an autosomal dominant dentin disorder. We recently generated a mouse model (named " mice") that expressed a mutant DSPP in which the proline residue at position 19 was replaced by a leucine residue. We found that the and mice at a younger age displayed a tooth phenotype resembling human DGI type III characterized by enlarged dental pulp chambers, while the teeth of older and mice had smaller dental pulp chambers mimicking DGI type II. The teeth of and mice had a narrower pulp chamber roof predentin layer, thinner pulp chamber roof dentin, and thicker pulp chamber floor dentin. In addition, these mice also had increased enamel attrition, accompanied by excessive deposition of peritubular dentin. Immunohistochemistry, in situ hybridization, and real-time polymerase chain reaction analyses showed that the odontoblasts in both and mice had reduced DSPP expression, compared to the wild-type mice. We also observed that the levels of DSPP expression were much higher in the roof-forming odontoblasts than in the floor-forming odontoblasts in the wild-type mice and mutant mice. Moreover, immunohistochemistry showed that while the immunostaining signals of dentin sialoprotein (N-terminal fragment of DSPP) were decreased in the dentin matrix, they were remarkably increased in the odontoblasts of the and mice. Consistently, our in vitro studies showed that the secretion of the mutant DSPP was impaired and accumulated within endoplasmic reticulum. These findings suggest that the dental phenotypes of the mutant mice were associated with the intracellular retention of the mutant DSPP in the odontoblasts of the DSPP-mutant mice.
Topics: Animals; Dentin; Dentinogenesis; Dentinogenesis Imperfecta; Disease Models, Animal; Extracellular Matrix Proteins; Humans; Mice; Odontoblasts; Phosphoproteins; Sialoglycoproteins
PubMed: 31173534
DOI: 10.1177/0022034519854029 -
International Endodontic Journal Feb 2013To summarize the collective in vitro, in vivo and clinical evidence of the involvement of the receptor activator of NF-κB ligand (RANKL)-osteoprotegerin (OPG) system, a... (Review)
Review
AIM
To summarize the collective in vitro, in vivo and clinical evidence of the involvement of the receptor activator of NF-κB ligand (RANKL)-osteoprotegerin (OPG) system, a system of two molecules controlling osteoclast differentiation and hard-tissue resorption, in pulpal and periapical pathophysiology.
METHODOLOGY
A systematic search related to RANKL and/or OPG and pulp or periapical disease was conducted on Medline, Biosis, Cochrane, Embase and Web of Science databases using keywords and controlled vocabulary. No language restriction was applied. Two independent reviewers first screened titles and abstracts and then the full texts that were initially included. The reference lists of the identified publications were examined for additional titles.
RESULTS
A total of 33 papers were identified. In vitro studies (N = 11) revealed that pulpal cells can be stimulated by various inflammatory agents to produce RANKL, whilst many studies did not consider the RANKL/OPG ratio. Animal studies (N = 9) mostly focused on the time course and development of periapical lesions in relation to the RANKL-OPG system. Levels of RANKL and OPG in the necrotizing pulp were not investigated. Human studies (N = 13) showed a steady-state expression of OPG in the odontoblast layer. Conflicting results have been reported regarding the role of RANKL in active apical periodontitis, again because the correlation of this molecule with its inhibitor (OPG) was often disregarded.
CONCLUSIONS
There is relatively little information currently available that would highlight the specific role of RANKL and OPG in pulpal and periapical disease. OPG may play a protective role against internal resorption, whilst an increased periapical RANKL/OPG ratio might indicate bone resorption.
Topics: Alveolar Bone Loss; Animals; Cells, Cultured; Humans; Mice; Odontoblasts; Osteoprotegerin; Periapical Periodontitis; Pulpitis; Rats; Receptor Activator of Nuclear Factor-kappa B
PubMed: 22900632
DOI: 10.1111/j.1365-2591.2012.02105.x -
International Journal of Biological... 2020Tooth development is a complex process that is regulated precisely by several signalling pathways and transcription factors. GATA-binding protein 4 (GATA4) is a DNA...
Tooth development is a complex process that is regulated precisely by several signalling pathways and transcription factors. GATA-binding protein 4 (GATA4) is a DNA binding transcription factor, and our previous study showed that GATA4 is a novel regulator of root development. However, it remains unclear whether GATA4 is necessary for odontoblast differentiation and dentin formation. Here, we evaluated the phenotypic changes of mice. The mutant mice showed defective dentin and short root deformity. The odontoblasts lost polarity instead of exhibiting a shorter height and flattened morphology. Moreover, the expression of several molecules, such as DSPP, COL-1, DCN, and PCNA, were downregulated during mutant tooth development. , we injected lentivirus to overexpress GATA4 in mice root. The dentin formation and the expression of odonto/osteogenic markers (DSPP, COL-1, DCN) were enhanced in the GATA4 overexpression group. During the study, the ability of proliferation, migration and odonto/osteogenic differentiation was declined by GATA4 knockdown approach in human dental pulp stem cells (DPSCs). The expression of odonto/osteogenic markers (DSPP, BMP4, RUNX2, OSX, OPN, OCN) was reduced in the shGATA4 group, while overexpressing GATA4 in DPSCs promoted mineralization. Furthermore, an immunoprecipitation-mass spectrometry procedure was used to confirm the interaction between GATA4 and Fructose-1, 6-bisphosphatase 1 (FBP1). We used gain and lose-of-function to delineated the role of GATA4 in regulating FBP1 expression. Knocking down GATA4 in DPSCs resulted in decreased glucose consumption and lactate production. We used small hairpin RNA targeting FBP1 to reduce the expression of FBP1 in DPSCs, which significantly increased glucose consumption and lactate production. Together, the results suggested that GATA4 is important for root formation and odontoblast polarity, as it promotes the growth and differentiation of dental mesenchymal cells around the root and affects the glucose metabolism of DPSCs the negative regulation of FBP1.
Topics: Animals; Cell Differentiation; Dentin; Dentinogenesis; Fructose-Bisphosphatase; GATA4 Transcription Factor; Gluconeogenesis; Mice, Knockout; Multipotent Stem Cells; Neural Crest; Odontoblasts; Tooth Root
PubMed: 31892855
DOI: 10.7150/ijbs.36567 -
Stem Cell Research & Therapy May 2023Signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3), a secreted multifunctional glycoprotein whose transcript expression is restricted to the tooth germ...
BACKGROUND
Signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3), a secreted multifunctional glycoprotein whose transcript expression is restricted to the tooth germ epithelium during the development of embryonic mouse teeth, has been demonstrated to play a crucial role in the regulation of tooth development. Based on this, we hypothesized that epithelium-derived SCUBE3 contributes to bio-function in dental mesenchymal cells (Mes) via epithelium-mesenchyme interactions.
METHODS
Immunohistochemical staining and a co-culture system were used to reveal the temporospatial expression of the SCUBE3 protein during mouse tooth germ development. In addition, human dental pulp stem cells (hDPSCs) were used as a Mes model to study the proliferation, migration, odontoblastic differentiation capacity, and mechanism of rhSCUBE3. Novel pulp-dentin-like organoid models were constructed to further confirm the odontoblast induction function of SCUBE3. Finally, semi-orthotopic animal experiments were performed to explore the clinical application of rhSCUBE3. Data were analysed using one-way analysis of variance and t-tests.
RESULTS
The epithelium-derived SCUBE3 translocated to the mesenchyme via a paracrine pathway during mouse embryonic development, and the differentiating odontoblasts in postnatal tooth germ subsequently secreted the SCUBE3 protein via an autocrine mechanism. In hDPSCs, exogenous SCUBE3 promoted cell proliferation and migration via TGF-β signalling and accelerated odontoblastic differentiation via BMP2 signalling. In the semi-orthotopic animal experiments, we found that SCUBE3 pre-treatment-induced polarized odontoblast-like cells attached to the dental walls and had better angiogenesis performance.
CONCLUSION
SCUBE3 protein expression is transferred from the epithelium to mesenchyme during embryonic development. The function of epithelium-derived SCUBE3 in Mes, including proliferation, migration, and polarized odontoblastic differentiation, and their mechanisms are elaborated for the first time. These findings shed light on exogenous SCUBE3 application in clinic dental pulp regeneration.
Topics: Animals; Humans; Mice; Dental Pulp; Embryonic Development; Regeneration; Mesenchymal Stem Cells; Cell Differentiation; Odontoblasts; Calcium-Binding Proteins
PubMed: 37189178
DOI: 10.1186/s13287-023-03353-0 -
Head & Face Medicine Dec 2017The revitalization or regeneration of the dental pulp is a preferable goal in current endodontic research. In this study, human dental pulp cell (DPC) spheres were...
BACKGROUND
The revitalization or regeneration of the dental pulp is a preferable goal in current endodontic research. In this study, human dental pulp cell (DPC) spheres were applied to human root canal samples to evaluate their potential adoption for physiological tissue-like regeneration of the dental root canal by odontoblastic differentiation as well as cell-induced mineral formation.
METHODS
DPC were cultivated into three-dimensional cell spheres and seeded on human root canal specimens. The evaluation of sphere formation, tissue-like behavior and differentiation as well as mineral formation of the cells was carried out with the aid of optical light microscopy, immunohistochemical staining and scanning electron microscopy (SEM).
RESULTS
Spheres and cells migrated out of the spheres showed an intense cell-cell- and cell-dentin-contact with the formation of extra cellular matrix. In addition, the ingrowth of cell processes into dentinal tubules and the interaction of cell processes with the tubule walls were detected by SEM-imaging. Immunohistochemical staining of the odontoblast specific matrix proteins, dentin matrix protein-1, and dentin sialoprotein revealed an odontoblast-like cell differentiation in contact with the dentin surface. This differentiation was confirmed by SEM-imaging of cells with an odontoblast specific phenotype and cell induced mineral formation.
CONCLUSIONS
The results of the present study reveal the high potential of pulp cells organized in spheres for dental tissue engineering. The odontoblast-like differentiation and the cell induced mineral formation display the possibility of a complete or partial "dentinal filling" of the root canal and the opportunity to combine this method with other current strategies.
Topics: Adult; Bicuspid; Cell Differentiation; Cell Movement; Dental Pulp; Dental Pulp Cavity; Dentin; Female; Humans; In Vitro Techniques; Male; Middle Aged; Minerals; Molar; Odontoblasts; Regeneration; Root Canal Therapy; Tissue Engineering; Tissue Scaffolds
PubMed: 29221472
DOI: 10.1186/s13005-017-0156-y