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Journal of Dental Research Apr 2023Root apical complex, including Hertwig's epithelial root sheath, apical papilla, and dental follicle (DF), is the germinal center of root development, wherein the DF...
Root apical complex, including Hertwig's epithelial root sheath, apical papilla, and dental follicle (DF), is the germinal center of root development, wherein the DF constantly develops into periodontal tissue. However, whether DF development is regulated by the adjacent apical papilla remains largely unknown. In this study, we employed a transwell coculture system and found that stem cells from the apical papilla (SCAPs) inhibit the differentiation and maintain the stemness of dental follicle stem cells (DFSCs). Meanwhile, partial SCAP differentiation markers were upregulated after DFSC coculture. High-throughput RNA sequencing revealed that the Hedgehog (Hh) pathway was significantly downregulated in DFSCs cocultured with SCAPs. Upregulation or downregulation of the Hh pathway can respectively activate or inhibit the multidirectional differentiation of DFSCs. Osteoglycin (OGN) (previously known as mimecan) is highly expressed in the dental papilla, similarly to Hh pathway factors. By secreting OGN, SCAP regulated the stemness and multidirectional differentiation of DFSCs via the OGN-Hh pathway. Finally, mice were established using the CRISPR/Cas9 system. We found that the root length growth rate was accelerated during root development from PN0 to PN30 in mice. Moreover, the hard tissues (including dentin and cementum) of the root in mice were thicker than those in wild-type mice. These phenotypes were likely due to Hh pathway activation and the increased cell proliferation and differentiation in both the apical papilla and DF. The current work elucidates the molecular regulation of early periodontal tissue development, providing a theoretical basis for future research on tooth root biology and periodontal tissue regeneration.
Topics: Animals; Mice; Cell Differentiation; Cell Proliferation; Cells, Cultured; Dental Cementum; Dental Papilla; Dental Sac; Hedgehog Proteins; Osteogenesis; Tooth; Tooth Root
PubMed: 36515316
DOI: 10.1177/00220345221138517 -
Journal of Endodontics May 2010Regenerative endodontic procedures use the differentiation potential of embryonic and adult pulp progenitor cell populations to reconstitute dental structures. (Review)
Review
INTRODUCTION
Regenerative endodontic procedures use the differentiation potential of embryonic and adult pulp progenitor cell populations to reconstitute dental structures.
METHODS
An in-depth search of the literature was accomplished to review biologic knowledge from basic research on tooth morphogenesis and differentiation, root development, dentin-pulp regeneration, pulp revascularization and apexification, experimental and clinical studies on the dentinogenic differentiation potential of progenitor cells in the embryonic dental papilla, dental pulp, and associated mesenchymal tissues of the developing root.
RESULTS
Odontogenic potential is determined during early tooth morphogenesis in the odontogenic mesenchyme. Progenitor cells from the odontogenic mesenchyme give rise to primary dentin-forming cells (odontoblasts) in the presence of stage-specific enamel epithelium and/or basement membrane and tertiary dentin-forming cells (odontoblast-like cells) in experimental conditions. The specificity of odontogenic mesenchymal cells to form tertiary dentin might be related to the repertoire of signaling pathways operated by the temporospatial pattern of epithelial-mesenchymal interactions during tooth formation. Dental papilla cells isolated from tooth germs before the onset of odontoblast differentiation have not shown any competence to become odontoblasts in the absence of enamel epithelium. On the other hand, the specificity of progenitor cells in the mesenchymal cell populations of the developing root apex remains to be determined.
CONCLUSIONS
It seems evident that the dental pulp might be only used as a source of progenitor cells with dentinogenic competence for the regeneration of the dentin-pulp complex. The nature of dental or apical papilla progenitor cells in terms of their specificity for dentin regeneration has to be first characterized.
Topics: Adult Stem Cells; Apexification; Cell Differentiation; Dental Papilla; Dental Pulp; Dentin, Secondary; Dentinogenesis; Humans; Mesenchymal Stem Cells; Neovascularization, Physiologic; Odontoblasts; Regeneration; Tooth Apex; Tooth Calcification
PubMed: 20416419
DOI: 10.1016/j.joen.2010.02.006 -
Journal of Dental Research Sep 2009To date, 5 different human dental stem/progenitor cells have been isolated and characterized: dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth... (Comparative Study)
Comparative Study Review
To date, 5 different human dental stem/progenitor cells have been isolated and characterized: dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), stem cells from apical papilla (SCAP), and dental follicle progenitor cells (DFPCs). These postnatal populations have mesenchymal-stem-cell-like (MSC) qualities, including the capacity for self-renewal and multilineage differentiation potential. MSCs derived from bone marrow (BMMSCs) are capable of giving rise to various lineages of cells, such as osteogenic, chondrogenic, adipogenic, myogenic, and neurogenic cells. The dental-tissue-derived stem cells are isolated from specialized tissue with potent capacities to differentiate into odontogenic cells. However, they also have the ability to give rise to other cell lineages similar to, but different in potency from, that of BMMSCs. This article will review the isolation and characterization of the properties of different dental MSC-like populations in comparison with those of other MSCs, such as BMMSCs. Important issues in stem cell biology, such as stem cell niche, homing, and immunoregulation, will also be discussed.
Topics: Bone Marrow Cells; Cell Differentiation; Cell Lineage; Dental Papilla; Dental Pulp; Dental Sac; Humans; Mesenchymal Stem Cells; Periodontal Ligament; Regeneration; Tissue Engineering; Tooth; Tooth, Deciduous
PubMed: 19767575
DOI: 10.1177/0022034509340867 -
Cell and Tissue Research Feb 2021The dental pulp, a non-mineralized connective tissue uniquely encased within the cavity of the tooth, provides a niche for diverse arrays of dental mesenchymal stem... (Review)
Review
The dental pulp, a non-mineralized connective tissue uniquely encased within the cavity of the tooth, provides a niche for diverse arrays of dental mesenchymal stem cells. Stem cells in the dental pulp, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHEDs) and stem cells from apical papilla (SCAPs), have been isolated from human tissues with an emphasis on their potential application to regenerative therapies. Recent studies utilizing mouse genetic models shed light on the identities of these mesenchymal progenitor cells derived from neural crest cells (NCCs) in their native conditions, particularly regarding how they contribute to homeostasis and repair of the dental tissue. The current concept is that at least two distinct niches for stem cells exist in the dental pulp, e.g., the perivascular niche and the perineural niche. The precise identities of these stem cells and their niches are now beginning to be unraveled thanks to sophisticated mouse genetic models, which lead to better understanding of the fundamental properties of stem cells in the dental pulp and the apical papilla in humans. The new knowledge will be highly instrumental for developing more effective stem cell-based regenerative therapies to repair teeth in the future.
Topics: Animals; Biomarkers; Dental Papilla; Dental Pulp; Mice; Models, Genetic; Stem Cell Niche; Stem Cells
PubMed: 32803323
DOI: 10.1007/s00441-020-03271-0 -
Recent Patents on DNA & Gene Sequences 2009A complex human tissue harbors stem cells that are responsible for its maintenance or repair. These stem cells have been isolated also from dental tissues such as the... (Review)
Review
A complex human tissue harbors stem cells that are responsible for its maintenance or repair. These stem cells have been isolated also from dental tissues such as the periodontal ligament, dental papilla or dental follicle and they may offer novel applications in dentistry. This following review summarizes patents about dental stem cells for dental tissue engineering and considers their value for regenerative dentistry.
Topics: Dental Papilla; Dental Pulp; Humans; Models, Biological; Neurons; Patents as Topic; Periodontal Ligament; Stem Cells; Technology, Dental; Tissue Engineering; Tooth
PubMed: 19149737
DOI: 10.2174/187221509787236200 -
Archives of Oral Biology Sep 2022The aim of this study was to test the hypothesis in vitro and in vivo, that the glycoprotein Wnt6 can regulate human dental papilla cell differentiation by β-catenin...
OBJECTIVE
The aim of this study was to test the hypothesis in vitro and in vivo, that the glycoprotein Wnt6 can regulate human dental papilla cell differentiation by β-catenin signaling.
DESIGN
The expression of Wnt6 was detected by quantitative polymerase chain reaction (qPCR). Wnt6 stealth RNA was used to knockdown the expression of Wnt6. The Wnt canonical signaling was detected by immunofluorescence staining, qPCR, and TOPflash/FOPflash dual-luciferase reporter assay. The differentiation was investigated by alkaline phosphatase staining or Alizarin Red staining after osteo/odontogenic medium culture and by Masson trichrome staining after subcutaneous transplantation. There are at least three samples in one group for each experiment.
RESULTS
Wnt6 protein and mRNA were high expressed in dental mesenchyme tissue and cells. In human dental papilla cells, Wnt6 over-expression could activate β-catenin dependent pathway, including β-catenin accumulation in cell nuclei, lymphoid enhancer factor 1 mRNA up-regulation, and enhanced β-catenin transcriptional activity. Wnt6 activated β-catenin pathway in a similar way to Wnt3a but at a lower level. Wnt6 inhibited human dental papilla cells differentiation as alkaline phosphatase activity in vitro, and promoted differentiation as mineralization after subcutaneous transplantation in vivo, as same trend as Wnt3a but at a lower level. The Wnt/β-catenin inhibitor XAV939 treatment attenuated Wnt6- or Wnt3a-induced human dental papilla cells mineralization.
CONCLUSIONS
Wnt6 activated β-catenin dependent pathway and regulated human dental papilla cells differentiation. Potential mechanism of Wnt6-regulated cell differentiation is the activation of Wnt/β-catenin signaling pathway.
Topics: Alkaline Phosphatase; Cell Differentiation; Dental Papilla; Glycoproteins; Humans; Osteogenesis; RNA, Messenger; Wnt Proteins; Wnt Signaling Pathway; beta Catenin
PubMed: 35691114
DOI: 10.1016/j.archoralbio.2022.105469 -
The International Journal of... May 2021SIRT4 is a mitochondrial sirtuin. Owing to its dependance on the cofactor nicotinamide adenine dinucleotide (NAD), SIRT4 can act as a mitochondrial metabolic sensor of...
INTRODUCTION
SIRT4 is a mitochondrial sirtuin. Owing to its dependance on the cofactor nicotinamide adenine dinucleotide (NAD), SIRT4 can act as a mitochondrial metabolic sensor of cellular energy status. We have previously shown that enhancement of mitochondrial functions is vital for the odontogenic diff ;erentiation of dental papilla cells (DPCs) during dentinogenesis. However, whether SIRT4 serves as an effective regulator of DPC diff ;erentiation by affecting mitochondrial functions remains unexplored.
METHODS
Primary DPCs obtained from the first molar dental papilla of neonatal Sprague-Dawley rats were used in this study. The expression pattern of SIRT4 was observed by immunohistochemistry in the first molar of postnatal day 1 (P1) rats. The changes in SIRT4 expression during odontogenic DPC differentiation were evaluated using real-time quantitative polymerase chain reaction (PCR), western blotting, and immunofluorescence. DPCs with loss (small interfering RNA-mediated knockdown) and gain (plasmid transfection-induced overexpression) of SIRT4 function were used to explore the role of SIRT4 in odontogenic differentiation. Mitochondrial function assays were performed using ATP, reactive oxygen species (ROS), and NAD/NADH kits to investigate the potential mechanisms involved in SIRT4-mediated dentinogenesis.
RESULTS
In the present study, we found that SIRT4 expression increased in a time-dependent manner during odontogenic differentiation bothin vivo and in vitro. Sirt4 knockdown resulted in reduced odontogenic differentiation and mineralization, whereas an opposite effect was observed with SIRT4 overexpression. Furthermore, our results verified that in addition to reducing DPC differentiation, Sirt4 knockdown could also significantly reduce ATP levels, elevate the NAD/NADH ratio, and increase ROS levels.
CONCLUSION
SIRT4 regulates mitochondrial functions and the antioxidant capacity of DPCs, thereby influencing dentin formation and tooth development, a phenomenon that may provide a foundation for better understanding the specific molecular mechanisms underlying dentin regeneration.
Topics: Animals; Animals, Newborn; Cell Differentiation; Dental Papilla; Mitochondria; Models, Animal; Odontogenesis; Primary Cell Culture; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Sirtuins
PubMed: 33636397
DOI: 10.1016/j.biocel.2021.105962 -
Developmental Biology Jun 2012At the bud stage of tooth development the neural crest derived mesenchyme condenses around the dental epithelium. As the tooth germ develops and proceeds to the cap...
At the bud stage of tooth development the neural crest derived mesenchyme condenses around the dental epithelium. As the tooth germ develops and proceeds to the cap stage, the epithelial cervical loops grow and appear to wrap around the condensed mesenchyme, enclosing the cells of the forming dental papilla. We have fate mapped the dental mesenchyme, using in vitro tissue culture combined with vital cell labelling and tissue grafting, and show that the dental mesenchyme is a much more dynamic population then previously suggested. At the bud stage the mesenchymal cells adjacent to the tip of the bud form both the dental papilla and dental follicle. At the early cap stage a small population of highly proliferative mesenchymal cells in close proximity to the inner dental epithelium and primary enamel knot provide the major contribution to the dental papilla. These cells are located between the cervical loops, within a region we have called the body of the enamel organ, and proliferate in concert with the epithelium to create the dental papilla. The condensed dental mesenchymal cells that are not located between the body of the enamel organ, and therefore are at a distance from the primary enamel knot, contribute to the dental follicle, and also the apical part of the papilla, where the roots will ultimately develop. Some cells in the presumptive dental papilla at the cap stage contribute to the follicle at the bell stage, indicating that the dental papilla and dental follicle are still not defined populations at this stage. These lineage-tracing experiments highlight the difficulty of targeting the papilla and presumptive odontoblasts at early stages of tooth development. We show that at the cap stage, cells destined to form the follicle are still competent to form dental papilla specific cell types, such as odontoblasts, and produce dentin, if placed in contact with the inner dental epithelium. Cell fate of the dental mesenchyme at this stage is therefore determined by the epithelium.
Topics: Animals; Cell Lineage; Dental Enamel; Dental Papilla; Mesoderm; Mice; Odontogenesis; Tooth
PubMed: 22542602
DOI: 10.1016/j.ydbio.2012.03.018 -
Brazilian Dental Journal 2011Dental pulp is a highly specialized mesenchymal tissue that has a limited regeneration capacity due to anatomical arrangement and post-mitotic nature of odontoblastic... (Review)
Review
Dental pulp is a highly specialized mesenchymal tissue that has a limited regeneration capacity due to anatomical arrangement and post-mitotic nature of odontoblastic cells. Entire pulp amputation followed by pulp space disinfection and filling with an artificial material cause loss of a significant amount of dentin leaving as life-lasting sequelae a non-vital and weakened tooth. However, regenerative endodontics is an emerging field of modern tissue engineering that has demonstrated promising results using stem cells associated with scaffolds and responsive molecules. Thereby, this article reviews the most recent endeavors to regenerate pulp tissue based on tissue engineering principles and provides insightful information to readers about the different aspects involved in tissue engineering. Here, we speculate that the search for the ideal combination of cells, scaffolds, and morphogenic factors for dental pulp tissue engineering may be extended over future years and result in significant advances in other areas of dental and craniofacial research. The findings collected in this literature review show that we are now at a stage in which engineering a complex tissue, such as the dental pulp, is no longer an unachievable goal and the next decade will certainly be an exciting time for dental and craniofacial research.
Topics: Adult Stem Cells; Animals; Dental Papilla; Dental Pulp; Humans; Induced Pluripotent Stem Cells; Intercellular Signaling Peptides and Proteins; Neovascularization, Physiologic; Odontoblasts; Periodontal Ligament; Regeneration; Tissue Engineering; Tissue Scaffolds; Tooth, Deciduous
PubMed: 21519641
DOI: 10.1590/s0103-64402011000100001 -
Journal of Dental Research Nov 2015Stem cells of the apical papilla (SCAP) represent great promise regarding treatment of neural tissue damage, such as spinal cord injury (SCI). They derive from the...
Stem cells of the apical papilla (SCAP) represent great promise regarding treatment of neural tissue damage, such as spinal cord injury (SCI). They derive from the neural crest, express numerous neurogenic markers, and mediate neurite outgrowth and axonal targeting. The goal of the present work was to investigate for the first time their potential to promote motor recovery after SCI in a rat hemisection model when delivered in their original stem cell niche-that is, by transplantation of the human apical papilla tissue itself into the lesion. Control groups consisted of animals subjected to laminectomy only (shams) and to lesion either untreated or injected with a fibrin hydrogel with or without human SCAP. Basso-Beattie-Bresnahan locomotor scores at 1 and 3 d postsurgery confirmed early functional decline in all SCI groups. This significant impairment was reversed, as seen in CatWalk analyses, after transplantation of apical papilla into the injured spinal cord wound, whereas the other groups demonstrated persistent functional impairment. Moreover, tactile allodynia did not develop as an unwanted side effect in any of the groups, even though the SCAP hydrogel group showed higher expression of the microglial marker Iba-1, which has been frequently associated with allodynia. Notably, the apical papilla transplant group presented with reduced Iba-1 expression level. Masson trichrome and human mitochondria staining showed the preservation of the apical papilla integrity and the presence of numerous human cells, while human cells could no longer be detected in the SCAP hydrogel group at the 6-wk postsurgery time point. Altogether, our data suggest that the transplantation of a human apical papilla at the lesion site improves gait in spinally injured rats and reduces glial reactivity. It also underlines the potential interest for the application of delivering SCAP in their original niche, as compared with use of a fibrin hydrogel.
Topics: Adolescent; Animals; Chronic Pain; Dental Papilla; Humans; Locomotion; Rats; Spinal Cord; Spinal Cord Injuries; Stem Cell Transplantation; Treatment Outcome
PubMed: 26341974
DOI: 10.1177/0022034515604612