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Proceedings. Biological Sciences Dec 2023Pronounced over-eruption of the canine teeth, causing the cervical enamel margin to extend beyond the alveolar bone and exposing the root, occurs with age and growth in...
Pronounced over-eruption of the canine teeth, causing the cervical enamel margin to extend beyond the alveolar bone and exposing the root, occurs with age and growth in Australian marsupial carnivores, much more than in eco-morphologically equivalent placental carnivores. Suppression of functional tooth replacement is characteristic of marsupials, where most placentals have the primitive diphyodont pattern of two generations of incisor, canine and premolar teeth. Canine and molar tooth dimensions of four species of marsupial carnivores (thylacine , Tasmanian devil and two quolls spp) and canine dimensions of seven eco-morphologically equivalent placental carnivore species were measured from museum specimens. Canine dimensions were measured in a time series on live wild-living individual devils and quolls. The canine teeth and to a lesser extent the molar teeth of marsupial carnivores continue to erupt through life, resulting in a net increase in tooth height and diameter, a phenomenon not evident in placental carnivores. Potential mechanisms causing over-eruption include tooth wear and gradual release of occlusal pressure as the individual grows. Over-eruption in marsupial carnivores may be a compensatory response for tooth size limits imposed by monophyodont tooth replacement, ensuring that animal's teeth are scaled to jaw size from juvenile to adulthood.
Topics: Pregnancy; Animals; Female; Marsupialia; Australia; Placenta; Odontogenesis
PubMed: 38087924
DOI: 10.1098/rspb.2023.0644 -
Journal of Endodontics Dec 2023This study aimed to evaluate the chemomechanical properties and biocompatibility of recently introduced premixed putty-type bioactive ceramic cements (PPBCs).
INTRODUCTION
This study aimed to evaluate the chemomechanical properties and biocompatibility of recently introduced premixed putty-type bioactive ceramic cements (PPBCs).
METHODS
Including ProRoot MTA (PMTA) as a control, BC RRM fast-set putty (BCPT), Well-Root PT (WRPT), One-Fil PT (OFPT), and Endocem MTA premixed (ECPM) were compared to evaluate setting time, radiopacity, pH change, and microhardness. Biocompatibility on human dental pulp cells was compared using CCK-8 assay. Mineralization potential was evaluated using alkaline phosphatase activity, Alizarin Red S (ARS) staining, and quantitative real-time polymerase chain reaction with odontogenic gene marker. For data analysis, 1-way analysis of variance and Tukey's post hoc test were used at the significance level of 95%.
RESULTS
Among the PPBCs, BCPT presented the longest (552 ± 27) setting time (minutes) and others showed significantly shorter time than PMTA (334 ± 22) (P < .05). WRPT (6.20 ± 0.54) and OFPT (5.82 ± 0.50) showed significantly higher radiopacity values (mmAl) and others showed similar value compared with PMTA (P > .05). All PPBCs showed high alkaline pH from fresh materials and tended to increase according to time periods from 30 minutes to 12 hours. ECPM showed the highest value of microhardness (81.62 ± 5.90), WRPT showed similar, and others showed lower than PMTA (P < .05). All PPBCs showed biocompatibility in CCK-8 assay. All PPBCs showed similar or better value compared with PMTA in ALP and ARS staining, and ALP and DSPP marker expression (P < .05).
CONCLUSIONS
The PPBCs showed clinically acceptable chemomechanical properties and favorable mineralization potential.
Topics: Humans; Calcium Compounds; Sincalide; Root Canal Filling Materials; Odontogenesis; Ceramics; Silicates; Oxides; Drug Combinations; Materials Testing; Aluminum Compounds; Dental Cements
PubMed: 37734586
DOI: 10.1016/j.joen.2023.09.005 -
Materials Today. Bio Apr 2024Human-treated dentin matrix (hTDM) has recently been studied as a natural extracellular matrix-based biomaterial for dentin pulp regeneration. However, porcine-treated...
BACKGROUND
Human-treated dentin matrix (hTDM) has recently been studied as a natural extracellular matrix-based biomaterial for dentin pulp regeneration. However, porcine-treated dentin matrix (pTDM) is a potential alternative scaffold due to limited availability. However, there is a dearth of information regarding the protein composition and underlying molecular mechanisms of pTDM.Methods: hTDM and pTDM were fabricated using human and porcine teeth, respectively, and their morphological characteristics were examined using scanning electron microscopy. Stem cells derived from human exfoliated deciduous teeth (SHEDs) were isolated and characterized using flow cytometry and multilineage differentiation assays. SHEDs were cultured in three-dimensional environments with hTDM, pTDM, or biphasic hydroxyapatite/tricalcium phosphate. The expression of odontogenesis markers in SHEDs were assessed using real-time polymerase chain reaction and immunochemical staining. Subsequently, SHEDs/TDM and SHEDs/HA/TCP complexes were transplanted subcutaneously into nude mice. The protein composition of pTDM was analyzed using proteomics and compared to previously published data on hTDM.Results: pTDM and hTDM elicited comparable upregulation of odontogenesis-related genes and proteins in SHEDs. Furthermore, both demonstrated the capacity to stimulate root-related tissue regeneration . Proteomic analysis revealed the presence of 278 protein groups in pTDM, with collagens being the most abundant. Additionally, pTDM and hTDM shared 58 identical proteins, which may contribute to their similar abilities to induce odontogenesis.
CONCLUSIONS
Both hTDM and pTDM exhibit comparable capabilities in inducing odontogenesis, potentially owing to their distinctive bioactive molecular networks.
PubMed: 38371466
DOI: 10.1016/j.mtbio.2024.100990 -
Beijing Da Xue Xue Bao. Yi Xue Ban =... Aug 2023To investigate the characteristics of exosomes derived from dental pulp stem cells (DPSCs) in the direction of odontogenic differentiation, to analyze the differences in...
OBJECTIVE
To investigate the characteristics of exosomes derived from dental pulp stem cells (DPSCs) in the direction of odontogenic differentiation, to analyze the differences in microRNA expression profile between exosomes derived from undifferentiated and odontogenic DPSCs, and to analyze their possible signal transduction pathways.
METHODS
(1) DPSCs were cultured in minimum Eagle' s medium (-MEM), and odontogenic DPSCs were cultured in odontogenic differentiation medium for 21 days, using alizarin red staining and alkaline phosphatase staining to identify the odontogenic differentiation. Exosomes from the cell supernatant were isolated respectively, named as dental pulp stem cells-exosomes (DPSCs-Exo) and dental pulp stem cells-odontogenic-exosomes (DPSCs-OD-Exo). The exosomes were identified by transmission electron microscopy, nanoparticle tracking analysis and Western blot. (2) The microRNA expression profiles of DPSCs-Exo and DPSCs-OD-Exo were investigated by microRNA microarray. To validate the result of the microRNA microarray, real-time quantitative polymerase chain reaction (real-time PCR) assay was applied on 3 most significantly differential expressed microRNA. Pathway analysis was taken to detect enriched pathways associated with the predicted target genes of microRNA.
RESULTS
(1) The DPSCs were isolated and cultured showed typical fibroblast-like morphology. The odontogenic differentiated DPSCs were spindle-shaped, polygonal, and uniform in size. Odontogenic differentiation group showed a large number of dark deposits in alizarin red staining and the cells were darkly stained in alkaline phosphatase staining, while the cells in normal culture medium group did not show obvious dyeing. The DPSCs-Exo and DPSCs-OD-Exo had the same morphology, both showed bilayer membrane and cup-shape. The peak sizes of DPSCs-Exo and DPSCs-OD-Exo were (114.67±9.07) nm and (134.00±8.54) nm, respectively. The difference between the two was statistically significant. DPSCs-Exo and DPSCs-OD-Exo both expressed the markers of exosomes, tumor susceptibility gene (TSG)101 and CD63. (2) microRNA microarray results showed that the expression profiles of DPSCs-Exo and DPSCs-OD-Exo were different. Nineteen increased by more than two times, and one decreased by 64%. Real-time PCR results showed that the expression levels of microRNA-1246, microRNA-1246-100-5p and microRNA-1246-494-3p in DPSCs-OD-Exo were significantly up-regulated. The difference was statistically significant. microRNA target prediction database and gene signaling pathway database were used to analyze differentially expressed microRNA, and it was predicted that differentially expressed microRNA could target axis inhibition protein 2() gene and Wnt/β-catenin signaling pathway.
CONCLUSION
DPSCs-OD-Exo and DPSCs-Exo had differences in their microRNA expression profile. Those differentially expressed microRNA may be involved in the regulation of DPSCs odontogenic differentiation.
Topics: Exosomes; Alkaline Phosphatase; Dental Pulp; Odontogenesis; Cell Differentiation; MicroRNAs; Stem Cells; Cells, Cultured; Cell Proliferation
PubMed: 37534653
DOI: 10.19723/j.issn.1671-167X.2023.04.020 -
Journal of Translational Medicine Jan 2024Revascularization and restoration of normal pulp-dentin complex are important for tissue-engineered pulp regeneration. Recently, a unique periodontal tip-like...
BACKGROUND
Revascularization and restoration of normal pulp-dentin complex are important for tissue-engineered pulp regeneration. Recently, a unique periodontal tip-like endothelial cells subtype (POTCs) specialized to dentinogenesis was identified. We have confirmed that TPPU, a soluble epoxide hydrolase (sEH) inhibitor targeting epoxyeicosatrienoic acids (EETs) metabolism, promotes bone growth and regeneration by angiogenesis and osteogenesis coupling. We hypothesized that TPPU could also promote revascularization and induce POTCs to contribute to pulp-dentin complex regeneration. Here, we in vitro and in vivo characterized the potential effect of TPPU on the coupling of angiogenesis and odontogenesis and investigated the relevant mechanism, providing new ideas for pulp-dentin regeneration by targeting sEH.
METHODS
In vitro effects of TPPU on the proliferation, migration, and angiogenesis of dental pulp stem cells (DPSCs), human umbilical vein endothelial cells (HUVECs) and cocultured DPSCs and HUVECs were detected using cell counting kit 8 (CCK8) assay, wound healing, transwell, tube formation and RT-qPCR. In vivo, Matrigel plug assay was performed to outline the roles of TPPU in revascularization and survival of grafts. Then we characterized the VEGFR2 + POTCs around odontoblast layer in the molar of pups from C57BL/6 female mice gavaged with TPPU. Finally, the root segments with DPSCs mixed with Matrigel were implanted subcutaneously in BALB/c nude mice treated with TPPU and the root grafts were isolated for histological staining.
RESULTS
In vitro, TPPU significantly promoted the migration and tube formation capability of cocultured DPSCs and HUVECs. ALP and ARS staining and RT-qPCR showed that TPPU promoted the osteogenic and odontogenic differentiation of cultured cells, treatment with an anti-TGF-β blocking antibody abrogated this effect. Knockdown of HIF-1α in HUVECs significantly reversed the effect of TPPU on the expression of angiogenesis, osteogenesis and odontogenesis-related genes in cocultured cells. Matrigel plug assay showed that TPPU increased VEGF/VEGFR2-expressed cells in transplanted grafts. TPPU contributed to angiogenic-odontogenic coupling featured by increased VEGFR2 + POTCs and odontoblast maturation during early dentinogenesis in molar of newborn pups from C57BL/6 female mice gavaged with TPPU. TPPU induced more dental pulp-like tissue with more vessels and collagen fibers in transplanted root segment.
CONCLUSIONS
TPPU promotes revascularization of dental pulp regeneration by enhancing migration and angiogenesis of HUVECs, and improves odontogenic differentiation of DPSCs by TGF-β. TPPU boosts the angiogenic-odontogenic coupling by enhancing VEGFR2 + POTCs meditated odontoblast maturation partly via upregulating HIF-1α, which contributes to increasing pulp-dentin complex for tissue-engineered pulp regeneration.
Topics: Mice; Animals; Female; Humans; Dental Pulp; Epoxide Hydrolases; Mice, Nude; Stem Cells; Mice, Inbred C57BL; Regeneration; Cells, Cultured; Human Umbilical Vein Endothelial Cells; Cell Differentiation; Dentin
PubMed: 38229161
DOI: 10.1186/s12967-024-04863-y -
Medecine Sciences : M/S Jan 2024Tooth formation results from specific epithelial-mesenchymal interactions, which summarize a number of developmental processes. Tooth anomalies may thus reflect...
Tooth formation results from specific epithelial-mesenchymal interactions, which summarize a number of developmental processes. Tooth anomalies may thus reflect subclinical diseases of the kidney, bone and more broadly of the mineral metabolism, skin or nervous system. Odontogenesis starts from the 3 week of intrauterine life by the odontogenic orientation of epithelial cells by a first PITX2 signal. The second phase is the acquisition of the number, shape, and position of teeth. It depends on multiple transcription and growth factors (BMP, FGF, SHH, WNT). These ecto-mesenchymal interactions guide cell migration, proliferation, apoptosis and differentiation ending in the formation of the specific dental mineralized tissues. Thus, any alteration will have consequences on the tooth structure or shape. Resulting manifestations will have to be considered in the patient phenotype and the multidisciplinary care, but also may contribute to identify the altered genetic circuity.
Topics: Humans; Epithelium; Signal Transduction; Tooth; Odontogenesis; Cell Differentiation; Gene Expression Regulation, Developmental
PubMed: 38299898
DOI: 10.1051/medsci/2023190 -
Biomedicines Feb 2024Exosomes derived from M2 macrophages (M2-Exos) exhibit tremendous potential for inducing tissue repair and regeneration. Herein, this study was designed to elucidate the...
Multifunctional Exosomes Derived from M2 Macrophages with Enhanced Odontogenesis, Neurogenesis and Angiogenesis for Regenerative Endodontic Therapy: An In Vitro and In Vivo Investigation.
INTRODUCTION
Exosomes derived from M2 macrophages (M2-Exos) exhibit tremendous potential for inducing tissue repair and regeneration. Herein, this study was designed to elucidate the biological roles of M2-Exos in regenerative endodontic therapy (RET) compared with exosomes from M1 macrophages (M1-Exos).
METHODS
The internalization of M1-Exos and M2-Exos by dental pulp stem cells (DPSCs) and human umbilical vein endothelial cells (HUVECs) was detected by uptake assay. The effects of M1-Exos and M2-Exos on DPSC and HUVEC behaviors, including migration, proliferation, odonto/osteogenesis, neurogenesis, and angiogenesis were determined in vitro. Then, Matrigel plugs incorporating M2-Exos were transplanted subcutaneously into nude mice. Immunostaining for vascular endothelial growth factor (VEGF) and CD31 was performed to validate capillary-like networks.
RESULTS
M1-Exos and M2-Exos were effectively absorbed by DPSCs and HUVECs. Compared with M1-Exos, M2-Exos considerably facilitated the proliferation and migration of DPSCs and HUVECs. Furthermore, M2-Exos robustly promoted ALP activity, mineral nodule deposition, and the odonto/osteogenic marker expression of DPSCs, indicating the powerful odonto/osteogenic potential of M2-Exos. In sharp contrast with M1-Exos, which inhibited the neurogenic capacity of DPSCs, M2-Exos contributed to a significantly augmented expression of neurogenic genes and the stronger immunostaining of Nestin. Consistent with remarkably enhanced angiogenic markers and tubular structure formation in DPSCs and HUVECs in vitro, the employment of M2-Exos gave rise to more abundant vascular networks, dramatically higher VEGF expression, and widely spread CD31 tubular lumens in vivo, supporting the enormous pro-angiogenic capability of M2-Exos.
CONCLUSIONS
The multifaceted roles of M2-Exos in ameliorating DPSC and HUVEC functions potentially contribute to complete functional pulp-dentin complex regeneration.
PubMed: 38398043
DOI: 10.3390/biomedicines12020441 -
Dentistry Journal Sep 2023Supernumerary teeth form at an incidence of about 3% in the population, with differences among races and various clinical consequences. Information on detailed patterns,...
Supernumerary teeth form at an incidence of about 3% in the population, with differences among races and various clinical consequences. Information on detailed patterns, and especially on white subjects, is scarce in the literature. Therefore, we aimed to investigate the patterns of non-syndromic permanent supernumerary teeth in a white European population. A record review was performed in different orthodontic clinics and identified 207 eligible individuals with 258 supernumerary teeth. Approximately 80% of the subjects had one supernumerary tooth, while 15% had two. Supernumerary tooth formation was more often evident in males (male/female: 1.65). However, there was no sexual dimorphism in its severity. The following pattern sequences, with decreasing prevalence order, were observed in the maxilla: 21 > 11 > 12 > 18 > 28 and in the mandible: 34 > 44 > 35 > 45 > 42. Supernumerary teeth were most often unilaterally present, without sexual dimorphism. In the maxilla, they were more often anteriorly present, whereas in the mandible, an opposite tendency was observed. Supernumerary teeth were consistently more often observed in the maxilla than in the mandible; 74% were impacted, 80% had normal orientation (13% horizontal, 7% inverted), and 53% had normal size. The present thorough supernumerary tooth pattern assessment enables a better understanding of this condition with clinical, developmental, and evolutionary implications.
PubMed: 37886915
DOI: 10.3390/dj11100230 -
Stem Cell Research & Therapy Sep 2023CDC42 is a member of Rho GTPase family, acting as a molecular switch to regulate cytoskeleton organization and junction maturation of epithelium in organ development....
BACKGROUND
CDC42 is a member of Rho GTPase family, acting as a molecular switch to regulate cytoskeleton organization and junction maturation of epithelium in organ development. Tooth root pattern is a highly complicated and dynamic process that dependens on interaction of epithelium and mesenchyme. However, there is a lack of understanding of the role of CDC42 during tooth root elongation.
METHODS
The dynamic expression of CDC42 was traced during tooth development through immunofluorescence staining. Then we constructed a model of lentivirus or inhibitor mediated Cdc42 knockdown in Herwig's epithelial root sheath (HERS) cells and dental papilla cells (DPCs), respectively. Long-term influence of CDC42 abnormality was assessed via renal capsule transplantation and in situ injection of alveolar socket.
RESULTS
CDC42 displayed a dynamic spatiotemporal pattern, with abundant expression in HERS cells and apical DPCs in developing root. Lentivirus-mediated Cdc42 knockdown in HERS cells didn't disrupt cell junctions as well as epithelium-mesenchyme transition. However, inhibition of CDC42 in DPCs undermined cell proliferation, migration and odontogenic differentiation. Wnt/β-catenin signaling as the downstream target of CDC42 modulated DPCs' odontogenic differentiation. The transplantation and in situ injection experiments verified that loss of CDC42 impeded root extension via inhibiting the proliferation and differentiation of DPCs.
CONCLUSIONS
We innovatively revealed that CDC42 was responsible for guiding root elongation in a mesenchyme-specific manner. Furthermore, CDC42-mediated canonical Wnt signaling regulated odontogenic differentiation of DPCs during root formation.
Topics: Female; Humans; Wnt Signaling Pathway; Cell Differentiation; Epithelial Cells; Epithelial-Mesenchymal Transition; Tooth Root
PubMed: 37726858
DOI: 10.1186/s13287-023-03486-2 -
Heliyon Dec 2023Alleviating inflammation and promoting dentine regeneration is critical for the healing of pulpitis. In this study, we investigated the anti-inflammatory, angiogenesis...
Alleviating inflammation and promoting dentine regeneration is critical for the healing of pulpitis. In this study, we investigated the anti-inflammatory, angiogenesis and odontogenesis function of icariin on Human dental pulp cells (HDPCs) under inflammatory state. Furthermore, the underlying mechanisms was also evaluated. Icariin attenuated the LPS-induced pro-inflammatory marker expression, such as interleukin-1β (IL-1β), IL-6 and IL-8. The immunoblotting and immunofluorescence staining results showed that icariin suppressed the inflammatory responses mediated by the protein kinase B (Akt) and nuclear factor kappa-B (NF-κB) signaling cascades. Additionally, icariin also upregulated the expression of odontogenic and angiogenic genes and proteins (namely dentin sialophosphoprotein (DSPP), dentin matrix protein 1 (DMP1), anti-collagen Ⅰ (COL-Ⅰ), and vascular endothelial growth factor (VEGF) and fibroblast growth factor-1 (FGF-1)), alkaline phosphatase activity, and calcium nodule deposition in LPS-exposed HDPCs. In a word, our findings indicated that icariin attenuated pulp inflammation and promoted odontogenic and angiogenic differentiation in the inflammatory state. Icariin may be a promising vital pulp therapy agent for the regenerative treatment of the inflamed dental pulp.
PubMed: 38144358
DOI: 10.1016/j.heliyon.2023.e23282