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Dentistry Journal Apr 2023Collagen is the building block for the extracellular matrix in bone, teeth and other fibrous tissues. Osteogenesis imperfecta (OI), or brittle bone disease, is a... (Review)
Review
Collagen is the building block for the extracellular matrix in bone, teeth and other fibrous tissues. Osteogenesis imperfecta (OI), or brittle bone disease, is a heritable disorder that results from defective collagen synthesis or metabolism, resulting in bone fragility. The dental manifestation of OI is dentinogenesis imperfecta (DI), a genetic disorder that affects dentin structure and clinical appearance, with a characteristic feature of greyish-brown discolouration. The aim of this study was to conduct a systematic review to identify and/or define any ultrastructural changes in dentinal collagen in DI. Established databases were searched: Cochrane Library, OVID Embase, OVID Medline and PubMed/Medline. Search strategies included: Collagen Ultrastructure, DI and OI. Inclusion criteria were studies written in English, published after 1990, that examined human dental collagen of teeth affected by DI. A Cochrane data extraction form was modified and used for data collection. The final dataset included seventeen studies published from 1993 to 2021. The most prevalent findings on collagen in DI teeth were increased coarse collagen fibres and decreased fibre quantity. Additional findings included changes to fibre orientation (i.e., random to parallel) and differences to the fibre organisation (i.e., regular to irregular). Ultrastructural defects and anomalies included uncoiled collagen fibres and increased D-banding periodicity. Studies in collagen structure in DI reported changes to the surface topography, quantity, organisation and orientation of the fibres. Moreover, ultrastructural defects such as the packing/coiling and D-banding of the fibrils, as well as differences in the presence of other collagens are also noted. Taken together, this study provides an understanding of the changes in collagen and its impact on clinical translation, paving the way for innovative treatments in dental treatment.
PubMed: 37185473
DOI: 10.3390/dj11040095 -
Stem Cell Research & Therapy Jul 2023Dental pulp stem cells (DPSCs) play a crucial role in dentin-pulp complex regeneration. Further understanding of the mechanism by which DPSCs remain in a quiescent state...
BACKGROUND
Dental pulp stem cells (DPSCs) play a crucial role in dentin-pulp complex regeneration. Further understanding of the mechanism by which DPSCs remain in a quiescent state could contribute to improvements in the dentin-pulp complex and dentinogenesis.
METHODS
TSC1 conditional knockout (DMP1-Cre+; TSC1, hereafter CKO) mice were generated to increase the activity of mechanistic target of rapamycin complex 1 (mTORC1). H&E staining, immunofluorescence and micro-CT analysis were performed with these CKO mice and littermate controls. In vitro, exosomes were collected from the supernatants of MDPC23 cells with different levels of mTORC1 activity and then characterized by transmission electron microscopy and nanoparticle tracking analysis. DPSCs were cocultured with MDPC23 cells and MDPC23 cell-derived exosomes. Alizarin Red S staining, ALP staining, qRT‒PCR, western blotting analysis and micro-RNA sequencing were performed.
RESULTS
Our study showed that mTORC1 activation in odontoblasts resulted in thicker dentin and higher dentin volume/tooth volume of molars, and it increased the expression levels of the exosome markers CD63 and Alix. In vitro, when DPSCs were cocultured with MDPC23 cells, odontoblastic differentiation was inhibited. However, the inhibition of odontoblastic differentiation was reversed when DPSCs were cocultured with MDPC23 cells with mTORC1 overactivation. To further study the effects of mTORC1 on exosome release from odontoblasts, MDPC23 cells were treated with rapamycin or shRNA-TSC1 to inactivate or activate mTORC1, respectively. The results revealed that exosome release from odontoblasts was negatively correlated with mTORC1 activity. Moreover, exosomes derived from MDPC23 cells with active or inactive mTORC1 inhibited the odontoblastic differentiation of DPSCs at the same concentration. miRNA sequencing analysis of exosomes that were derived from shTSC1-transfected MDPC23 cells, rapamycin-treated MDPC23 cells or nontreated MDPC23 cells revealed that the majority of the miRNAs were similar among these groups. In addition, exosomes derived from odontoblasts inhibited the odontoblastic differentiation of DPSCs, and the inhibitory effect was positively correlated with exosome concentration.
CONCLUSION
mTORC1 regulates exosome release from odontoblasts to inhibit the odontoblastic differentiation of DPSCs, but it does not alter exosomal contents. These findings might provide a new understanding of dental pulp complex regeneration.
Topics: Mice; Animals; Odontoblasts; Extracellular Matrix Proteins; Dental Pulp; Exosomes; Cell Differentiation; Stem Cells; Cells, Cultured
PubMed: 37422687
DOI: 10.1186/s13287-023-03401-9 -
BioMed Research International 2022Portland cement (PC) is used in challenging endodontic situations in which preserving the health and functionality of pulp tissue is of considerable importance. PC forms... (Review)
Review
Portland cement (PC) is used in challenging endodontic situations in which preserving the health and functionality of pulp tissue is of considerable importance. PC forms the main component of mineral trioxide aggregate (MTA) and demonstrates similar desirable properties as an orthograde or retrograde filling material. PC is able to protect pulp against bacterial infiltration, induce reparative dentinogenesis, and form dentin bridge during the pulp healing process. The biocompatibility, bioactivity, and physical properties of PC have been investigated and in animal models, as well as in some limited clinical trials. This paper reviews Portland cement's structure and its characteristics and reaction in various environments and eventually accentuates the present concerns with this material. This bioactive endodontic cement has shown promising success rates compared to MTA; however, considerable modifications are required in order to improve its characteristics and expand its application scope as a root repair material. Hence, the extensive chemical modifications incorporated into PC composition to facilitate preparation and handling procedures are discussed. It is still important to further address the applicability, reliability, and cost-effectiveness of PC before transferring into day-to-day clinical practice.
Topics: Aluminum Compounds; Animals; Biocompatible Materials; Calcium Compounds; Dental Cements; Drug Combinations; Humans; Oxides; Root Canal Filling Materials; Silicates
PubMed: 35036431
DOI: 10.1155/2022/3314912 -
Frontiers in Cell and Developmental... 2021Embryonic development and stem cell differentiation are orchestrated by changes in sequential binding of regulatory transcriptional factors to their motifs. These...
Embryonic development and stem cell differentiation are orchestrated by changes in sequential binding of regulatory transcriptional factors to their motifs. These processes are invariably accompanied by the alternations in chromatin accessibility, conformation, and histone modification. Odontoblast lineage originates from cranial neural crest cells and is crucial in dentinogenesis. Our previous work revealed several transcription factors (TFs) that promote odontoblast differentiation. However, it remains elusive as to whether chromatin accessibility affects odontoblast terminal differentiation. Herein, integration of single-cell RNA-seq and bulk RNA-seq revealed that odontoblast differentiation using dental papilla cells at E18.5 was comparable to the crown odontoblast differentiation trajectory of OC (osteocalcin)-positive odontogenic lineage. Before odontoblast differentiation, ATAC-seq and H3K27Ac CUT and Tag experiments demonstrated high accessibility of chromatin regions adjacent to genes associated with odontogenic potential. However, following odontoblastic induction, regions near mineralization-related genes became accessible. Integration of RNA-seq and ATAC-seq results further revealed that the expression levels of these genes were correlated with the accessibility of nearby chromatin. Time-course ATAC-seq experiments further demonstrated that odontoblast terminal differentiation was correlated with the occupation of the basic region/leucine zipper motif (bZIP) TF family, whereby we validated the positive role of ATF5 . Collectively, this study reports a global mapping of open chromatin regulatory elements during dentinogenesis and illustrates how these regions are regulated via dynamic binding of different TF families, resulting in odontoblast terminal differentiation. The findings also shed light on understanding the genetic regulation of dentin regeneration using dental mesenchymal stem cells.
PubMed: 34901015
DOI: 10.3389/fcell.2021.769193 -
Global Medical Genetics Sep 2021Dentin sialophosphoprotein ( ) gene mutations cause autosomal dominantly inherited diseases. gene mutations lead to abnormal expression of DSPP, resulting in a series... (Review)
Review
Dentin sialophosphoprotein ( ) gene mutations cause autosomal dominantly inherited diseases. gene mutations lead to abnormal expression of DSPP, resulting in a series of histological, morphological, and clinical abnormalities. A large number of previous studies demonstrated that DSPP is a dentinal-specific protein, and gene mutations lead to dentin dysplasia and dentinogenesis imperfecta. Recent studies have found that DSPP is also expressed in bone, periodontal tissues, and salivary glands. DSPP is involved in the formation of the periodontium as well as tooth structures. DSPP deficient mice present furcation involvement, cementum, and alveolar bone defect. We speculate that similar periodontal damage may occur in patients with mutations. This article reviewed the effects of gene mutations on periodontal status. However, almost all of the research is about animal study, there is no evidence that mutations cause periodontium defects in patients yet. We need to conduct systematic clinical studies on mutation families in the future to elucidate the effect of gene on human periodontium.
PubMed: 34430959
DOI: 10.1055/s-0041-1726416 -
International Journal of Dentistry 2021Dentinogenesis imperfecta (DI) and amelogenesis imperfecta (AI) are hereditary abnormalities of dental hard tissues. Dental abnormalities may also be accompanied by... (Review)
Review
Dentinogenesis imperfecta (DI) and amelogenesis imperfecta (AI) are hereditary abnormalities of dental hard tissues. Dental abnormalities may also be accompanied by symptoms of disorders such as osteogenesis imperfecta. AI and DI have a significant burden on socializing, function, and comfort; therefore, frequent screening and accurate diagnosis is the cornerstone of managing such conditions. Both AI and DI could be treated with many strategies, including restorative, prosthetic, periodontal, surgical, and orthodontics treatment. The interdisciplinary combination of orthodontic, prosthodontic, and periodontic treatment has been proven to improve the prognosis of AI and DI. Regarding orthodontic treatment, the most difficult element of orthodontic therapy may be maintaining a high level of motivation for what might be a prolonged form of treatment spanning several years. There are many forms of orthodontic management for AI and DI, including removable appliances, functional appliances, and fixed appliances. Clear aligner therapy (CAT) contains a broad range of equipment that works in different ways, has different construction processes, and is compatible with different malocclusion procedures. The application of CAT in patients with AI and DI is favorable over the fixed applicants. However, the available evidence regarding the application of CAT in AI is weak and heterogeneous. In this review, we discussed the current evidence regarding the application of clear CAT in patients with AI and DI.
PubMed: 34976063
DOI: 10.1155/2021/7343094 -
Frontiers in Cell and Developmental... 2023Dental mesenchymal stem cells (DMSCs) are multipotent progenitor cells that can differentiate into multiple lineages including odontoblasts, osteoblasts, chondrocytes,... (Review)
Review
Dental mesenchymal stem cells (DMSCs) are multipotent progenitor cells that can differentiate into multiple lineages including odontoblasts, osteoblasts, chondrocytes, neural cells, myocytes, cardiomyocytes, adipocytes, endothelial cells, melanocytes, and hepatocytes. Odontoblastic differentiation of DMSCs is pivotal in dentinogenesis, a delicate and dynamic process regulated at the molecular level by signaling pathways, transcription factors, and posttranscriptional and epigenetic regulation. Mutations or dysregulation of related genes may contribute to genetic diseases with dentin defects caused by impaired odontoblastic differentiation, including tricho-dento-osseous (TDO) syndrome, X-linked hypophosphatemic rickets (XLH), Raine syndrome (RS), hypophosphatasia (HPP), Schimke immuno-osseous dysplasia (SIOD), and Elsahy-Waters syndrome (EWS). Herein, recent progress in the molecular regulation of the odontoblastic differentiation of DMSCs is summarized. In addition, genetic syndromes associated with disorders of odontoblastic differentiation of DMSCs are discussed. An improved understanding of the molecular regulation and related genetic syndromes may help clinicians better understand the etiology and pathogenesis of dentin lesions in systematic diseases and identify novel treatment targets.
PubMed: 37818127
DOI: 10.3389/fcell.2023.1174579 -
Journal of Clinical Medicine Jul 2021The dental pulp is a soft connective tissue of ectomesenchymal origin that harbors distinct cell populations, capable of interacting with each other to maintain the... (Review)
Review
The dental pulp is a soft connective tissue of ectomesenchymal origin that harbors distinct cell populations, capable of interacting with each other to maintain the vitality of the tooth. After tooth injuries, a sequence of complex biological events takes place in the pulpal tissue to restore its homeostasis. The pulpal response begins with establishing an inflammatory reaction that leads to the formation of a matrix of reactionary or reparative dentin, according to the nature of the exogenous stimuli. Using several in vivo designs, antigen-presenting cells, including macrophages and dendritic cells (DCs), are identified in the pulpal tissue before tertiary dentin deposition under the afflicted area. However, the precise nature of this phenomenon and its relationship to inherent pulp cells are not yet clarified. This literature review aims to discuss the role of pulpal DCs and their relationship to progenitor/stem cells, odontoblasts or odontoblast-like cells, and other immunocompetent cells during physiological and pathological dentinogenesis. The concept of "dentin-pulp immunology" is proposed for understanding the crosstalk among these cell types after tooth injuries, and the possibility of immune-based therapies is introduced to accelerate pulpal healing after exogenous stimuli.
PubMed: 34362130
DOI: 10.3390/jcm10153348 -
Frontiers in Cell and Developmental... 2023
PubMed: 36711029
DOI: 10.3389/fcell.2023.1138621 -
Frontiers in Physiology 2023Regenerative dentistry has rapidly progressed since the advancement of stem cell biology and material science. However, more emphasis has been placed on the success of... (Review)
Review
Regenerative dentistry has rapidly progressed since the advancement of stem cell biology and material science. However, more emphasis has been placed on the success of tissue formation than on how well the newly generated tissue retains the original structure and function. Once dentin is lost, tertiary dentinogenesis can be induced by new odontoblastic differentiation or re-activation of existing odontoblasts. The characteristic morphology of odontoblasts generates the tubular nature of dentin, which is a reservoir of fluid, ions, and a number of growth factors, and protects the inner pulp tissue. Therefore, understanding the dynamic but delicate process of new dentin formation by odontoblasts, or odontoblast-like cells, following dentinal defects is crucial. In this regard, various efforts have been conducted to identify novel molecules and materials that can promote the regeneration of dentin with strength and longevity. In this review, we focus on recent progress in dentin regeneration research with biological molecules identified, and discuss its potential in future clinical applications.
PubMed: 38148896
DOI: 10.3389/fphys.2023.1313927