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Journal of Endodontics May 2024Heparan sulfate (HS) is a major component of dental pulp tissue. We previously reported that inhibiting HS biosynthesis impedes endothelial differentiation of dental...
INTRODUCTION
Heparan sulfate (HS) is a major component of dental pulp tissue. We previously reported that inhibiting HS biosynthesis impedes endothelial differentiation of dental pulp stem cells (DPSCs). However, the underlying mechanisms by which exogenous HS induces DPSC differentiation and pulp tissue regeneration remain unknown. This study explores the impact of exogenous HS on vasculogenesis and dentinogenesis of DPSCs both in vitro and in vivo.
METHODS
Human-derived DPSCs were cultured in endothelial and odontogenic differentiation media and treated with HS. Endothelial differentiation of DPSCs was investigated by real-time polymerase chain reaction and capillary sprouting assay. Odontogenic differentiation was assessed through real-time polymerase chain reaction and detection of mineralized dentin-like deposition. Additionally, the influence of HS on pulp tissue was assessed with a direct pulp capping model, in which HS was delivered to exposed pulp tissue in rats. Gelatin sponges were loaded with either phosphate-buffered saline or 10-10 μg/mL HS and placed onto the pulp tissue. Following a 28-day period, tissues were investigated by histological analysis and micro-computed tomography imaging.
RESULTS
HS treatment markedly increased expression levels of key endothelial and odontogenic genes, enhanced the formation of capillary-like structures, and promoted the deposition of mineralized matrices. Treatment of exposed pulp tissue with HS in the in vivo pulp capping study induced formation of capillaries and reparative dentin.
CONCLUSIONS
Exogenous HS effectively promoted vasculogenesis and dentinogenesis of DPSCs in vitro and induced reparative dentin formation in vivo, highlighting its therapeutic potential for pulp capping treatment.
PubMed: 38719089
DOI: 10.1016/j.joen.2024.04.015 -
Cells Jul 2023The odontoblastic differentiation of dental pulp stem cells (DPSCs) associated with caries injury happens in an inflammatory context. We recently demonstrated that there...
The odontoblastic differentiation of dental pulp stem cells (DPSCs) associated with caries injury happens in an inflammatory context. We recently demonstrated that there is a link between inflammation and dental tissue regeneration, identified via enhanced DPSC-mediated dentinogenesis in vitro. Brain-derived neurotrophic factor (BDNF) is a nerve growth factor-related gene family molecule which functions through tropomyosin receptor kinase B (TrkB). While the roles of BDNF in neural tissue repair and other regeneration processes are well identified, its role in dentinogenesis has not been explored. Furthermore, the role of BDNF receptor-TrkB in inflammation-induced dentinogenesis remains unknown. The role of BDNF/TrkB was examined during a 17-day odontogenic differentiation of DPSCs. Human DPSCs were subjected to odontogenic differentiation in dentinogenic media treated with inflammation inducers (LTA or TNFα), BDNF, and a TrkB agonist (LM22A-4) and/or antagonist (CTX-B). Our data show that BDNF and TrkB receptors affect the early and late stages of the odontogenic differentiation of DPSCs. Immunofluorescent data confirmed the expression of BDNF and TrkB in DPSCs. Our ELISA and qPCR data demonstrate that TrkB agonist treatment increased the expression of dentin matrix protein-1 (DMP-1) during early DPSC odontoblastic differentiation. Coherently, the expression levels of runt-related transcription factor 2 (RUNX-2) and osteocalcin (OCN) were increased. TNFα, which is responsible for a diverse range of inflammation signaling, increased the levels of expression of dentin sialophosphoprotein (DSPP) and DMP1. Furthermore, BDNF significantly potentiated its effect. The application of CTX-B reversed this effect, suggesting TrkB`s critical role in TNFα-mediated dentinogenesis. Our studies provide novel findings on the role of BDNF-TrkB in the inflammation-induced odontoblastic differentiation of DPSCs. This finding will address a novel regulatory pathway and a therapeutic approach in dentin tissue engineering using DPSCs.
Topics: Humans; Tumor Necrosis Factor-alpha; Receptor, trkB; Tropomyosin; Brain-Derived Neurotrophic Factor; Dental Pulp; Cell Differentiation; Inflammation; Stem Cells
PubMed: 37508514
DOI: 10.3390/cells12141851 -
The Journal of Clinical Pediatric... 2019Dentinogenesis Imperfecta type II (DI2), also known as hereditary opalescent dentin, is one of the most common genetic disorders affecting the structure of dentin, not... (Review)
Review
Dentinogenesis Imperfecta type II (DI2), also known as hereditary opalescent dentin, is one of the most common genetic disorders affecting the structure of dentin, not related with osteogenesis imperfecta, which involves both primary and permanent dentitions. The purpose of this article is to perform a scoping review of the published peer-reviewed literature (1986-2017) on DI2 management in children and to outline the most relevant clinical findings extracted from this review. Forty four articles were included in the present scoping review. According to the extracted data, the following are the most important tasks to be performed in clinical pediatric dentistry: to re-establish the oral mastication, esthetics, and speech, and the development of vertical growth of alveolar bone and facial muscles; to reduce the tendency to develop caries, periapical lesions and pain; to preserve vitality, form, and size of the dentition; to avoid interfering with the eruption process of permanent teeth; to decrease the risk of tooth fractures and occlusion disturbances; to return the facial profile to a more normal appearance; and to prevent or treat possible temporomandibular joint problems. Therefore, Pediatric Dentists should bear in mind that early diagnosis and treatment, together a long-term follow-up of DI2 in children, continue to be the best approaches for achieving enhanced patient psychological well-being and, in consequence, their quality of life.
Topics: Child; Child, Preschool; Dental Care for Children; Dentinogenesis Imperfecta; Dentition, Permanent; Esthetics, Dental; Humans; Quality of Life
PubMed: 30964718
DOI: 10.17796/1053-4625-43.3.1 -
Medicina Oral, Patologia Oral Y Cirugia... May 2020The primordial odontogenic tumor (POT) is a recently described benign entity with histopathological and immunohistochemical features suggesting its origin during early...
BACKGROUND
The primordial odontogenic tumor (POT) is a recently described benign entity with histopathological and immunohistochemical features suggesting its origin during early odontogenesis.
AIM
To integrate the available data published on POT into a comprehensive analysis to better define its clinicopathological and molecular features.
MATERIAL AND METHODS
An electronic systematic review was performed up to September 2019 in multiple databases.
RESULTS
A total of 13 publications were included, representing 16 reported cases and 3 molecular studies. The mean age of the affected patients was 11.6 years (range 2-19), with a slight predominance in males (56.25%). The posterior mandible was the main location (87.5%), with only two cases affecting the posterior maxilla. All cases appeared as a radiolucent lesion in close relationship to an unerupted tooth. Recurrences have not been reported to date. Microscopically, POT comprises fibromyxoid tissue with variable cellularity surrounded by a cuboidal to columnar odontogenic epithelium but without unequivocal dental hard tissue formation. A delicate fibrous capsule surrounds (at least partially) the tumor. The epithelial component shows immunohistochemical positivity for amelogenin, CK19, and CK14, and variable expression of Glut-1, Galectin-3 and Caveolin-1, Vimentin, p-53, PITX2, Bcl-2, Bax and Survivin; the mesenchymal tissue is positive for Vimentin, CD90, p-53, PITX2, Bcl-2, Bax, and Survivin, and the subepithelial region exhibits the strong expression of Syndecan-1 and CD34. The Ki-67 index is low (<5%). The negative or weak expression of dentinogenesis-associated genes could explain the inhibition of dentin and subsequent enamel formation in this neoplasm.
CONCLUSION
POT is an entity with a well-defined clinicopathological, immunohistochemical and molecular profile that must be properly diagnosed and differentiated from other odontogenic lesions and treated consequently.
Topics: Adolescent; Adult; Child; Child, Preschool; Epithelium; Humans; Male; Mandible; Neoplasm Recurrence, Local; Odontogenesis; Odontogenic Tumors; Young Adult
PubMed: 32040459
DOI: 10.4317/medoral.23432 -
Bone Jun 2021Dental anomalies in Osteogenesis imperfecta (OI), such as tooth discoloration, pulp obliteration (calcified dental pulp space), and taurodontism (enlarged dental pulp...
INTRODUCTION
Dental anomalies in Osteogenesis imperfecta (OI), such as tooth discoloration, pulp obliteration (calcified dental pulp space), and taurodontism (enlarged dental pulp space) vary between and within patients. To better understand the associations and variations in these anomalies, a cross-sectional study was designed to analyze the dental phenotype in OI patients at the individual tooth type.
METHOD
A cohort of 171 individuals with OI type I, III and IV, aged 3-55 years, were recruited and evaluated for tooth discoloration, pulp obliteration, and taurodontism at the individual tooth level, using intraoral photographs and panoramic radiographs.
RESULTS
Genetic variants were identified in 154 of the participants. Patients with Helical α1 and α2 glycine substitutions presented the highest prevalence of tooth discoloration, while those with α1 Haploinsufficiency had the lowest (<10%). C-propeptide variants did not cause discoloration but resulted in the highest pulp obliteration prevalence (~%20). The prevalence of tooth discoloration and pulp obliteration was higher in OI types III and IV and increased with age. Tooth discoloration was mainly observed in teeth known to have thinner enamel (i.e. lower anterior), while pulp obliteration was most prevalent in the first molars. A significant association was observed between pulp obliteration and tooth discoloration, and both were associated with a lack of occlusal contact. Taurodontism was only found in permanent teeth and affected mostly first molars, and its prevalence decreased with age.
CONCLUSION
The dental phenotype evaluation at the tooth level revealed that different genetic variants and associated clinical phenotypes affect each tooth type differently, and genetic variants are better predictors of the dental phenotype than the type of OI. Our results also suggest that tooth discoloration is most likely an optical phenomenon inversely proportional to enamel thickness, and highly associated with pulp obliteration. In turn, pulp obliteration is proportional to patient age, it is associated with malocclusion and likely related to immature progressive dentin deposition. Taurodontism is an isolated phenomenon that is probably associated with delayed pulpal maturation.
Topics: Cross-Sectional Studies; Dentinogenesis Imperfecta; Humans; Osteogenesis Imperfecta; Phenotype; Tooth
PubMed: 33741542
DOI: 10.1016/j.bone.2021.115917 -
Journal of Cellular Biochemistry Mar 2020Cellular differentiation is caused by highly controlled modifications in the gene expression but rarely involves a change in the DNA sequence itself. Histone acetylation...
Cellular differentiation is caused by highly controlled modifications in the gene expression but rarely involves a change in the DNA sequence itself. Histone acetylation is a major epigenetic factor that adds an acetyl group to histone proteins, thus altering their interaction with DNA and nuclear proteins. Illumination of the histone acetylation during dentinogenesis is important for odontoblast differentiation and dentinogenesis. In the current study, we aimed to discover the roles and regulation of acetylation at histone 3 lysine 9 (H3K9ac) and H3K27ac during dentinogenesis. We first found that both of these modifications were enhanced during odontoblast differentiation and dentinogenesis. These modifications are dynamically catalyzed by histone acetyltransferases (HATs) and deacetylases (HDACs), among which HDAC3 was decreased while p300 increased during odontoblast differentiation. Moreover, overexpression of HDAC3 or knockdown p300 inhibited odontoblast differentiation in vitro, and inhibition of HDAC3 and p300 with trichostatin A or C646 regulated odontoblast differentiation. Taken together, the results of our present study suggest that histone acetylation is involved in dentinogenesis and coordinated expression of p300- and HDAC3-regulated odontoblast differentiation through upregulating histone acetylation.
Topics: Acetylation; Animals; Cell Differentiation; Cell Proliferation; Cells, Cultured; Dental Papilla; Dentinogenesis; E1A-Associated p300 Protein; Histone Deacetylases; Histones; Mesenchymal Stem Cells; Mice; Protein Processing, Post-Translational
PubMed: 31692090
DOI: 10.1002/jcb.29470 -
Journal of the Korean Association of... Apr 2017Nuclear factor I-C (NFI-C) plays a pivotal role in various cellular processes such as odontoblast and osteoblast differentiation. -deficient mice showed abnormal tooth... (Review)
Review
Nuclear factor I-C (NFI-C) plays a pivotal role in various cellular processes such as odontoblast and osteoblast differentiation. -deficient mice showed abnormal tooth and bone formation. The transplantation of -expressing mouse bone marrow stromal cells rescued the impaired bone formation in mice. Studies suggest that NFI-C regulate osteogenesis and dentinogenesis in concert with several factors including transforming growth factor-β1, Krüppel-like factor 4, and β-catenin. This review will focus on the function of NFI-C during tooth and bone formation and on the relevant pathways that involve NFI-C.
PubMed: 28462188
DOI: 10.5125/jkaoms.2017.43.2.63 -
Journal of Dentistry Apr 2022This study aims to review systematically the dental pulp response to silver diamine fluoride (SDF) treatment, including the inflammatory response, pulp cells activity,... (Review)
Review
OBJECTIVE
This study aims to review systematically the dental pulp response to silver diamine fluoride (SDF) treatment, including the inflammatory response, pulp cells activity, dentinogenesis, silver penetration, and the presence of the bacteria in the dental pulp.
DATA
In vitro studies, animal studies, clinical studies, and case reports on the use of SDF on vital dental pulp were included. Quality assessment of the included studies was conducted. A narrative synthesis of the collected data was performed.
SOURCES
A systematic search was performed in ProQuest, PubMed, SCOPUS, and Web of Science databases for articles published from inception to Nov 1, 2021.
STUDY SELECTION
The initial search identified 1,433 publications, of which five publications met the inclusion criteria. These five publications reported the effect of direct/ indirect SDF application on the vital pulp of a total of 30 teeth. Direct SDF application on vital pulp caused pulp necrosis. Indirect SDF application caused none or mild inflammatory response of dental pulp. The odontoblasts in the dental pulp showed increased cellular activity. Tertiary dentine was formed in the pulpal side of the cavity with indirect SDF application. Accentuated incremental lines of tertiary dentine reflected disturbances in mineralisation. Silver ions were found to penetrate along the dentinal tubules but were not detected inside the pulp.
CONCLUSION
According to the limited available literature, direct SDF application causes pulp necrosis. Indirect SDF application is generally biocompatible to dental pulp tissue with a mild inflammatory response, increased odontoblastic activity, and increased tertiary dentine formation. Future studies with precise quantitative and qualitative tests, larger sample size and longer follow-up time are imperative to understand the biological activity of dental pulp to SDF treatment.
Topics: Animals; Dental Caries; Dental Pulp; Dental Pulp Necrosis; Dentin, Secondary; Fluorides, Topical; Quaternary Ammonium Compounds; Silver Compounds
PubMed: 35139409
DOI: 10.1016/j.jdent.2022.104066 -
Biochimica Et Biophysica Acta.... Mar 2023The mandible is an important component of the craniofacial bones, whose development is regulated by complex molecular networks and involves the well-coordinated...
The mandible is an important component of the craniofacial bones, whose development is regulated by complex molecular networks and involves the well-coordinated development of the bone, cartilage, and teeth. Previously, we demonstrated that Krüppel-like factor 4 (KLF4) promoted dentinogenesis and osteogenesis, but it was enigmatic whether Klf4 participated in the development of the mandible. In this study, the Sp7-Cre; Klf4 mice exhibited underdeveloped mandibles and insufficient elongation of the mandibular incisor when compared with Klf4 and Sp7-Cre mice. Moreover, morphological and molecular analysis showed that the alveolar bone mass was significantly decreased in KLF4 deficient mice, accompanied by reduced expression of osteoblast-related genes. Meanwhile, the KLF4 deficient mice had decreased expression of receptor activator of nuclear factor kappa-Β ligand (RANKL) and no significant change of osteoprotegerin (OPG) in the alveolar bone near the mandibular incisor. Simultaneously, the osteoclastogenesis in the alveolar bone of KLF4 deficient mice was attenuated, which was demonstrated by a diminished number of tartrate-resistant acid phosphatase positive (TRAP+), matrix metallopeptidase 9 positive (MMP9+), and cathepsin K positive (CTSK+) multinucleated osteoclasts, respectively. Collectively, our study suggested that Klf4 participated in mandibular development, and Klf4 in Sp7+ lineage affected osteogenesis directly and osteoclastogenesis indirectly.
Topics: Mice; Animals; Glycoproteins; Incisor; Acid Phosphatase; Haploinsufficiency; Mandible; Sp7 Transcription Factor
PubMed: 36584722
DOI: 10.1016/j.bbadis.2022.166636 -
International Journal of Oral Science Nov 2018Phosphophoryn (PP) and dentin sialoprotein (DSP) are the most dominant non-collagenous proteins in dentin. PP is an extremely acidic protein that can function as a... (Review)
Review
Phosphophoryn (PP) and dentin sialoprotein (DSP) are the most dominant non-collagenous proteins in dentin. PP is an extremely acidic protein that can function as a mineral nucleator for dentin mineralization. DSP was first identified in 1981, yet its functional significance is still controversial. Historically, these two proteins were considered to be independently synthesized and secreted by dental pulp cells into the developing dentin matrix. However, with the identification of the DSP coding sequence in 1994, followed 2 years later by the finding that the PP coding sequence was located immediately downstream from the DSP sequence, it became immediately clear that DSP and PP proteins were derived from a single DSP-PP (i.e., dentin sialophosphoprotein, DSPP) transcript. Since DSPP cDNA became available, tremendous progress has been made in studying DSP-PP mRNA distribution and DSP generation from the DSP-PP precursor protein at specific cleavage sites by protease tolloid-related-1 (TLR1) or bone morphogenetic protein 1 (BMP1). The functions of DSP-PP and DSP were investigated via DSP-PP knockout (KO) and DSP knockin in DSP-PP KO mice. In addition, a number of in vitro studies aimed to elucidate DSPP and DSP function in dental pulp cells.
Topics: Animals; Dentinogenesis; Extracellular Matrix Proteins; Humans; Mice; Phosphoproteins; Sialoglycoproteins
PubMed: 30393383
DOI: 10.1038/s41368-018-0035-9