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Journal of Clinical and Experimental... Jan 2023Using dental implants to replacing missing teeth and satisfy both functional and aesthetic needs is one of the mainstream dental treatments. New approaches including... (Review)
Review
BACKGROUND
Using dental implants to replacing missing teeth and satisfy both functional and aesthetic needs is one of the mainstream dental treatments. New approaches including computer-aided design and computer-assisted manufacture (CAD/CAM) have been introduced to improve these elements. This systematic review aimed to compare CAD/CAM zirconia (Zr) implant abutments with other available abutments in terms of peri-implant health and aesthetics.
MATERIAL AND METHODS
Five electronic databases (PubMed, Web of Science, Scopus, ProQuest, and Embase) were scoured for clinical studies evaluating Zr abutments reporting on the outcomes of interest including interproximal papilla stability (PS), papilla recession (REC), pink and white esthetic score (PES, WES), marginal bone level (MBL), color, and soft tissue contour. A hand searches in English language journals until September 2020 complemented the search. Two tools of Joanna Briggs Institute and Jaded Score calculation were used for the risk of bias assessment. No quantitative synthesis of the data was done due to high heterogeneity.
RESULTS
A total of six studies from the 412 ones obtained from the search were included. The study designs were either prospective cohort (n=3) or randomized clinical trial (n=3). Papilla fill, WES, PES, and the distance from the bone crest of adjacent teeth to the contact point (CPB) and inter-tooth-implant distance (ITD) was not significantly different between Zr CAD/CAM and Zr stock abutments. However, soft tissue stability and REC index were better in Zr CAD/CAM abutments.
CONCLUSIONS
Higher soft tissue stability can be achieved for Zr compared to titanium abutments with either stock or CAD/CAM abutments. Dental implants, Dental abutment, Computer-Assisted Design, Computer-Aided Manufacturing, Zirconia abutment, Soft tissue stability.
PubMed: 36755676
DOI: 10.4317/jced.59878 -
Journal of Advanced Research Sep 2022Basic fibroblast growth factor (bFGF) plays a critical role in odontoblast differentiation and dentin matrix deposition, thereby aiding pulpo-dentin repair and...
bFGF stimulated plasminogen activation factors, but inhibited alkaline phosphatase and SPARC in stem cells from apical Papilla: Involvement of MEK/ERK, TAK1 and p38 signaling.
INTRODUCTION
Basic fibroblast growth factor (bFGF) plays a critical role in odontoblast differentiation and dentin matrix deposition, thereby aiding pulpo-dentin repair and regeneration.
OBJECTIVES
The purpose of this study was to clarify the effects of bFGF on plasminogen activation factors, TIMP-1), ALP; and SPARC (osteonectin) expression/production of stem cells from apical papilla (SCAP) in vitro; and the involvement of MEK/ERK, p38, Akt, and TAK1 signaling.
METHODS
SCAP were exposed to bFGF with/without pretreatment and co-incubation with various signal transduction inhibitors (U0126, SB203580, LY294002, and 5Z-7-oxozeaenol). The expression of FGF receptors (FGFRs), PAI-1, uPA, p-ERK, p-TAK1, and p-p38 was analyzed via immunofluorescent staining. The gene expression and protein secretion of SCAP were determined via real-time PCR and ELISA. ALP activity was evaluated via ALP staining.
RESULTS
SCAP expressed FGFR1, 2, 3, and 4. bFGF stimulated the PAI-1, uPA, uPAR, and TIMP-1 mRNA expression (p < 0.05). bFGF induced PAI-1, uPA, and soluble uPAR production (p < 0.05) but suppressed the ALP activity and SPARC production (p < 0.05) of SCAP. bFGF stimulated ERK, TAK1, and p38 phosphorylation of SCAP. U0126 (a MEK/ERK inhibitor) and 5Z-7-oxozeaenol (a TAK1 inhibitor) attenuated the bFGF-induced PAI-1, uPA, uPAR, and TIMP-1 expression and production of SCAP, but SB203580 (a p38 inhibitor) did not. LY294002, SB203580, and 5Z-7oxozeaenol could not reverse the inhibition of ALP activity caused by bFGF. Interestingly, U0126 and 5Z-7-oxozeaenol prevented the bFGF-induced decline of SPARC production (p < 0.05).
CONCLUSION
bFGF may regulate fibrinolysis and matrix turnover via modulation of PAI-1, uPA, uPAR, and TIMP-1, but bFGF inhibited the differentiation (ALP, SPARC) of SCAP. These events are mainly regulated by MEK/ERK, p38, and TAK1. Combined use of bFGF and SCAP may facilitate pulpal/root repair and regeneration via regulation of the plasminogen activation system, migration, matrix turnover, and differentiation of SCAP.
Topics: Alkaline Phosphatase; Butadienes; Fibroblast Growth Factor 2; Lactones; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase Kinases; Nitriles; Osteonectin; Plasminogen; Plasminogen Activator Inhibitor 1; Resorcinols; Signal Transduction; Stem Cells; Tissue Inhibitor of Metalloproteinase-1; Zearalenone
PubMed: 36100336
DOI: 10.1016/j.jare.2021.12.006 -
Journal of Oral Biosciences Jun 2024This study aimed to investigate the regulatory mechanisms governing dental mesenchymal cell commitment during tooth development, focusing on odontoblast differentiation...
Exploring the Role of DNMT1 in Dental Papilla Cell Fate Specification during Mouse Tooth Germ Development through Integrated Single-Cell Transcriptomics and Bulk RNA Sequencing.
OBJECTIVES
This study aimed to investigate the regulatory mechanisms governing dental mesenchymal cell commitment during tooth development, focusing on odontoblast differentiation and the role of epigenetic regulation in this process.
METHODS
We performed single-cell RNA sequencing (scRNA-seq) of dental cells from embryonic day 14.5 (E14.5) mice to understand the heterogeneity of developing tooth germ cells. Computational analyses including gene regulatory network (GRN) assessment were conducted. We validated our findings using immunohistochemistry (IHC) and in vitro loss-of-function analyses using the DNA methyltransferase 1 (DNMT1) inhibitor Gsk-3484862 in primary dental mesenchymal cells (DMCs) isolated from E14.5 mouse tooth germs. Bulk RNA-seq of Gsk-3484862-treated DMCs was performed to identify potential downstream targets of DNMT1.
RESULTS
scRNA-seq analysis revealed diverse cell populations within the tooth germs, including epithelial, mesenchymal, immune, and muscle cells. Using single-cell regulatory network inference and clustering (SCENIC), we identified Dnmt1 as a key regulator of early odontoblast development. IHC analysis showed the ubiquitous expression of DNMT1 in the dental papilla and epithelium. Bulk RNA-seq of cultured DMCs showed that Gsk-3484862 treatment upregulated odontoblast-related genes, whereas genes associated with cell division and the cell cycle were downregulated. Integrated analysis of bulk RNA-seq data with scRNA-seq SCENIC profiles was used to identify the potential Dnmt1 target genes.
CONCLUSIONS
Dnmt1 may negatively affect odontoblast commitment and differentiation during tooth development. These findings contribute to a better understanding of the molecular mechanisms underlying tooth development and future development of hard-tissue regenerative therapies.
PubMed: 38942194
DOI: 10.1016/j.job.2024.06.010 -
Frontiers in Cell and Developmental... 2019Fibroblast activation protein-α (FAPα) is a membrane protein with dipeptidyl-peptidase and type I collagenase activity and is expressed during fetal growth. At the age...
Fibroblast activation protein-α (FAPα) is a membrane protein with dipeptidyl-peptidase and type I collagenase activity and is expressed during fetal growth. At the age of adolescence, FAPα expression is greatly reduced, only emerging in pathologies associated with extracellular matrix remodeling. We determined whether FAPα is expressed in human dental tissue involved in root maturation i.e., dental follicle and apical papilla and in dental pulp tissue. The dental follicle revealed a high concentration of FAPα and vimentin-positive cells within the stromal tissue. A similar observation was made in cell culture and FACS analysis confirmed these as dental follicle stem cells. Within the remnants of the Hertwigs' epithelial root sheath, we observed FAPα staining in the E-cadherin positive and vimentin-negative epithelial islands. FAPα- and vimentin-positive cells were encountered at the periphery of the islands suggesting an epithelial mesenchymal transition process. Analysis of the apical papilla revealed two novel histological regions; the periphery with dense and parallel aligned collagen type I defined as cortex fibrosa and the inner stromal tissue composed of less compacted collagen defined as medulla. FAPα expression was highly present within the medulla suggesting a role in extracellular matrix remodeling. Dental pulp tissue uncovered a heterogeneous FAPα staining but strong staining was noted within odontoblasts. studies confirmed the presence of FAPα expression in stem cells of the apical papilla and dental pulp. This study identified the expression of FAPα expression in dental stem cells which could open new perspectives in understanding dental root maturation and odontoblast function.
PubMed: 32039205
DOI: 10.3389/fcell.2019.00389 -
Stem Cell Research & Therapy Feb 2022Commitment of mouse dental papilla cells (mDPCs) to the odontoblast lineage is critical for dentin formation, and this biological process is regulated by a complex...
BACKGROUND
Commitment of mouse dental papilla cells (mDPCs) to the odontoblast lineage is critical for dentin formation, and this biological process is regulated by a complex transcription factor network. The transcription factor Mycn is a proto-oncogene that plays an important role in tumorigenesis and normal embryonic development. An early study revealed that Mycn is exclusively expressed in dental mesenchymal cells at E15.5, which implies a potential role of Mycn in dentinogenesis. However, the role of Mycn in dentin formation remains elusive. Thus, it is of considerable interest to elucidate the role of Mycn in dentin formation.
METHODS
Mycn; Osr2 (Mycn) and Mycn; K14 (Mycn) transgenic mice were generated, and micro-CT scans were performed to quantitatively analyse the volumetric differences in the molars and incisors of the mutants and their littermates. Mycn was also knocked down in vitro, and alkaline phosphatase (ALP) and alizarin red staining (ARS) were conducted. Cleavage under targets and tagmentation (CUT&Tag) analysis and dual luciferase assays were performed to identify direct downstream targets of Mycn. Immunofluorescence and immunochemistry staining and western blotting (WB) were performed to analyse the expression levels of potential targets. Quantitative PCR, WB, ALP and ARS were performed to test the rescue efficiency.
RESULTS
Mesenchymal ablation of Mycn (Mycn) led to defective dentin formation, while epithelial deletion (Mycn) had no obvious effects on tooth development. ALP and ARS staining revealed that the commitment capacity of mDPCs to the odontoblast lineage was compromised in Mycn mice. CUT&Tag analysis identified Klf4 as a potential direct target of Mycn, and a dual luciferase reporter assay verified that Mycn could bind to the promotor region of Klf4 and directly activate its transcription. Reciprocally, forced expression of Klf4 partially recovered the odontoblastic differentiation capacity of mDPCs with Mycn knockdown.
CONCLUSIONS
Our results elucidated that mesenchymal Mycn modulates the odontoblastic commitment of dental papilla cells by directly regulating Klf4. Our study illustrated the role of Mycn in dentin development and furthers our general comprehension of the transcription factor networks involved in the dentinogenesis process. Thus, these results may provide new insight into dentin hypoplasia and bioengineered dentin regeneration.
Topics: Animals; Cell Differentiation; Kruppel-Like Factor 4; Mice; N-Myc Proto-Oncogene Protein; Odontoblasts; Odontogenesis; Transcription Factors
PubMed: 35193672
DOI: 10.1186/s13287-022-02749-8 -
Scientific Reports May 2022Melatonin plays a critical role in promoting the proliferation of osteoblasts and the growth and development of dental papilla cells. However, the effect and mechanism...
Melatonin plays a critical role in promoting the proliferation of osteoblasts and the growth and development of dental papilla cells. However, the effect and mechanism of melatonin on the growth and development of ALCs still need to be explored. CCK8 assay was used for the evaluation of cell numbers. qRT-PCR was used to identify the differentially expressed genes in ALCs after melatonin treatment. The number and morphology of ALCs were investigated by confocal microscopy. Alkaline phosphatase assay and Alizarin red S staining were used for measuring mineralization. Then, we focused on observing the crucial factors of the signaling pathway by RNA-seq and qRT-PCR. Melatonin limited the cell number of ALCs in a dose-dependent manner and promoted the production of actin fibers. A high concentration of melatonin significantly promoted the mRNA levels of enamel matrix proteins and the formation of mineralized nodules. RNA-seq data showed that Wnt signaling pathway may be involved in the differentiation of ALCs under the influence of melatonin. This study suggests that melatonin plays a regulatory role in the cell number, differentiation, and mineralization of the ALCs, and then shows the relationship between the Wnt signaling pathway with the ALCs under melatonin.
Topics: Ameloblasts; Animals; Cell Differentiation; Cell Line; Cell Proliferation; Melatonin; Mice; Osteoblasts; Osteogenesis; Wnt Signaling Pathway
PubMed: 35581244
DOI: 10.1038/s41598-022-11912-3 -
Journal of Dental Research Feb 2020Collagen signaling is critical for proper bone and tooth formation. Discoidin domain receptor 2 (DDR2) is a collagen-activated tyrosine kinase receptor shown to be...
Collagen signaling is critical for proper bone and tooth formation. Discoidin domain receptor 2 (DDR2) is a collagen-activated tyrosine kinase receptor shown to be essential for skeletal development. Patients with loss of function mutations in develop spondylo-meta-epiphyseal dysplasia (SMED), a rare, autosomal recessive disorder characterized by short stature, short limbs, and craniofacial anomalies. A similar phenotype was observed in -deficient mice, which exhibit dwarfism and defective bone formation in the axial, appendicular, and cranial skeletons. However, it is not known if has a role in tooth formation. We first defined the expression pattern of during tooth formation using knock-in mice. expression was detected in the dental follicle/sac and dental papilla mesenchyme of developing teeth and in odontoblasts and the periodontal ligament (PDL) of adults. No LacZ staining was detected in wild-type littermates. This expression pattern suggests a potential role in the tooth and surrounding periodontium. To uncover the function of , we used mice, which contain a spontaneous 150-kb deletion in the locus to produce an effective null. In comparison with wild-type littermates, mice displayed disproportional tooth size (decreased root/crown ratio), delayed tooth root development, widened PDL space, and interradicular alveolar bone defects. mice also had abnormal collagen content associated with upregulation of periostin levels within the PDL. The delayed root formation and periodontal abnormalities may be related to defects in RUNX2-dependent differentiation of odontoblasts and osteoblasts; RUNX2-S319-P was reduced in PDLs from mice, and deletion of in primary cell cultures from dental pulp and PDL inhibited differentiation of cells to odontoblasts or osteoblasts, respectively. Together, our studies demonstrate odontoblast- and PDL-specific expression of in mature and immature teeth, as well as indicate that DDR2 signaling is important for normal tooth formation and maintenance of the surrounding periodontium.
Topics: Animals; Discoidin Domain Receptor 2; Discoidin Domain Receptors; Humans; Mice; Odontogenesis; Receptor Protein-Tyrosine Kinases; Receptors, Mitogen
PubMed: 31869264
DOI: 10.1177/0022034519892563 -
PeerJ 2023Dental papilla cells (DPCs) are one of the key stem cells for tooth development, eventually forming dentin and pulp. Previous studies have reported that PER2 is...
BACKGROUND
Dental papilla cells (DPCs) are one of the key stem cells for tooth development, eventually forming dentin and pulp. Previous studies have reported that PER2 is expressed in a 24-hour oscillatory pattern in DPCs . , PER2 is highly expressed in odontoblasts (which are differentiated from DPCs). However, whether PER2 modulates the odontogenic differentiation of DPCs is uncertain. This research was to identify the function of PER2 in the odontogenic differentiation of DPCs and preliminarily explore its mechanisms.
METHODS
We monitored the expression of PER2 in DPCs differentiated . We used PER2 overexpression and knockdown studies to assess the role of PER2 in DPC differentiation and performed intracellular ATP content and reactive oxygen species (ROS) assays to further investigate the mechanism.
RESULTS
PER2 expression was considerably elevated throughout the odontoblastic differentiation of DPCs . Overexpressing boosted levels of odontogenic differentiation markers, such as dentin sialophosphoprotein (), dentin matrix protein 1 (), and alkaline phosphatase (), and enhanced mineralized nodule formation in DPCs. Conversely, the downregulation of inhibited the differentiation of DPCs. Additionally, downregulating further affected intracellular ATP content and ROS levels during DPC differentiation.
CONCLUSION
Overall, we demonstrated that PER2 positively regulates the odontogenic differentiation of DPCs, and the mechanism may be related to mitochondrial function as shown by intracellular ATP content and ROS levels.
Topics: Reactive Oxygen Species; Dental Papilla; Cell Differentiation; Odontoblasts; Adenosine Triphosphate
PubMed: 38084142
DOI: 10.7717/peerj.16489 -
Journal of Dentistry (Shiraz, Iran) Sep 2023The occurrence of papillary defects adjacent to teeth or dental implants causes both the dental staff and the patients to be concerned about the esthetic issues....
STATEMENT OF THE PROBLEM
The occurrence of papillary defects adjacent to teeth or dental implants causes both the dental staff and the patients to be concerned about the esthetic issues. Interdental papilla reconstruction surgery is one of the most difficult and unpredictable mucogingival surgeries.
PURPOSE
The present study aimed to investigate the efficacy of hyaluronic acid injection in the reconstruction of the interdental papilla.
MATERIALS AND METHOD
This clinical trial study was conducted on four patients with 20 deficient interdental papillae who met the inclusion criteria. At first, local anesthesia was applied. Afterward, 0.2 mL of 1.6% hyaluronic acid (HA) gel was injected (at the tip of the papilla and 2-3 mm below the tip of the papilla) three times every two weeks. At baseline, three, and six months later, clinical photography was taken under standard conditions. The papilla height (the distance between the interdental papilla tip and the basis), black triangle area, and the distance between the interdental papilla tip and contact point of adjacent teeth were all measured using Image J software.
RESULTS
The effectiveness of using HA gel in reducing the black triangle area was 85.06%. Furthermore, the papilla length increased by 70.256% while contact to papilla distance decreased by 83.026%. At different times, the values of the studied variables in the three levels were significantly different (< 0.05).
CONCLUSION
Injection of HA with 1.6% concentration at two points of the interdental papilla was effective in interdental papilla reconstruction at the aesthetic zone, especially in long-term, follow-ups (especially 6 months).
PubMed: 37727351
DOI: 10.30476/dentjods.2022.94766.1808 -
Turkish Journal of Orthodontics Dec 2019The purpose of the present study was to determine the facial anatomical landmarks, in order of accuracy, closest to the midline of the face, as well as oral cavity...
OBJECTIVE
The purpose of the present study was to determine the facial anatomical landmarks, in order of accuracy, closest to the midline of the face, as well as oral cavity midline, and to specify which intraoral anatomical landmarks are closer to the dental midline.
METHODS
Three commonly used anatomical landmarks including nasion, nose, and philtrum tips were marked clinically in 108 subjects. A frontal full-face digital image was used for midline analysis in accordance with the esthetic frame. Deviations from the facial and oral midlines were measured for the three clinical landmarks. Dental midline was considered as the fourth landmark. Alginate impressions were taken, and casts were analyzed under standardized conditions. The labial frenum and incisive papilla were marked. Cast images were taken and analyzed.
RESULTS
Data showed difference between the mean ratios of the selected anatomical landmarks and the facial and oral midlines (p≤0/05). The anatomical landmark hierarchies, in proximity to the facial midline, are commissural midlines, nasion, philtrum tip, nose tip, and dental midline, respectively. The anatomical landmark hierarchies, in proximity to the commissural midline, include dental midline, philtrum tip, nose tip, and nasion. The labial frenum was less deviated from the dental midline than the incisive papilla.
CONCLUSION
With respect to shortcomings, the results showed that all of the anatomical landmarks were deviated from the facial and oral midlines. The order of proximity of the anatomical landmarks to the facial midline was as follows: commissural midline, nasion, philtrum, and dental midline.
PubMed: 32110464
DOI: 10.5152/TurkJOrthod.2019.18086