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Swiss Dental Journal 2016
Topics: Animals; Dental Caries; Dental Pulp Capping; Dentin; Dentinogenesis; Humans; Microscopy, Electron, Scanning; Odontoblasts
PubMed: 27874915
DOI: No ID Found -
Frontiers in Physiology 2020Dentin sialoprotein (DSP), the NH2-terminal fragment of dentin sialophosphoprotein (DSPP), is essential for dentin formation and further processed into small fragments...
Dentin sialoprotein (DSP), the NH2-terminal fragment of dentin sialophosphoprotein (DSPP), is essential for dentin formation and further processed into small fragments inside the odontoblasts. Gelatinases, including matrix metalloproteinases 9 (MMP9) and MMP2, were able to cleave DSP(P) in tooth structures. We hypothesized that gelatinases may also cleave DSP intracellularly in the odontoblasts. In this study, the co-expression and physical interaction between DSP and gelatinases were proved by double immunofluorescence and proximity ligation assay (PLA). Intracellular enzymatic activity of gelatinases was verified by gelatin zymography and zymography. To confirm whether DSP was cleaved by active gelatinases intracellularly, lysates of odontoblastic cells treated with a MMP2 inhibitor or a MMP9 inhibitor or a MMP general inhibitor and of odontoblastic cells were analyzed by western blotting. Compared with the odontoblastic cells without inhibitor treatment, all these groups exhibited significantly higher ratios of high molecular weight to low molecular weight band density. FURIN was verified to be co-localized and physically interacted with MMP9 by double immunofluorescence and PLA. The ratio of proMMP9 to activated MMP9 inside the odontoblastic cells were increased when function of endogenous FURIN was inhibited. And overexpressed proMMP9 was intracellularly cleaved by FURIN in the HEK293E cells, which was completely blocked by the mutation of proMMP9 with RTPR substituted by AAAA. Taken together, these results indicate that DSP is intracellularly processed by gelatinases, and FURIN is involved in the intracellular activation of proMMP9 through cleavage of its RTPR motif.
PubMed: 32670089
DOI: 10.3389/fphys.2020.00686 -
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 -
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 -
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 -
Journal of Translational Medicine May 2022Sclerostin is the protein product of the SOST gene and is known for its inhibitory effects on bone formation. The monoclonal antibody against sclerostin has been... (Review)
Review
Sclerostin is the protein product of the SOST gene and is known for its inhibitory effects on bone formation. The monoclonal antibody against sclerostin has been approved as a novel treatment method for osteoporosis. Oral health is one of the essential aspects of general human health. Hereditary bone dysplasia syndrome caused by sclerostin deficiency is often accompanied by some dental malformations, inspiring the therapeutic exploration of sclerostin in the oral and dental fields. Recent studies have found that sclerostin is expressed in several functional cell types in oral tissues, and the expression level of sclerostin is altered in pathological conditions. Sclerostin not only exerts similar negative outcomes on the formation of alveolar bone and bone-like tissues, including dentin and cementum, but also participates in the development of oral inflammatory diseases such as periodontitis, pulpitis, and peri-implantitis. This review aims to highlight related research progress of sclerostin in oral cavity, propose necessary further research in this field, and discuss its potential as a therapeutic target for dental indications and regenerative dentistry.
Topics: Bone and Bones; Dentistry; Humans; Inflammation; Osteogenesis; Osteoporosis
PubMed: 35562828
DOI: 10.1186/s12967-022-03417-4 -
Journal of Dental Research Jan 2022Small-molecule drugs targeting glycogen synthase kinase 3 (GSK3) as inhibitors of the protein kinase activity are able to stimulate reparative dentine formation. To...
Small-molecule drugs targeting glycogen synthase kinase 3 (GSK3) as inhibitors of the protein kinase activity are able to stimulate reparative dentine formation. To develop this approach into a viable clinical treatment for exposed pulp lesions, we synthesized a novel, small-molecule noncompetitive adenosine triphosphate (ATP) drug that can be incorporated into a biodegradable hydrogel for placement by syringe into the tooth. This new drug, named NP928, belongs to the thiadiazolidinone (TDZD) family and has equivalent activity to similar drugs of this family such as tideglusib. However, NP928 is more water soluble than other TDZD drugs, making it more suitable for direct delivery into pulp lesions. We have previously reported that biodegradable marine collagen sponges can successfully deliver TDZD drugs to pulp lesions, but this involves in-theater preparation of the material, which is not ideal in a clinical context. To improve surgical handling and delivery, here we incorporated NP928 into a specifically tailored hydrogel that can be placed by syringe into a damaged tooth. This hydrogel is based on biodegradable hyaluronic acid and can be gelled in situ upon dental blue light exposure, similarly to other common dental materials. NP928 released from hyaluronic acid-based hydrogels upregulated Wnt/β-catenin activity in pulp stem cells and fostered reparative dentine formation compared to marine collagen sponges delivering equivalent concentrations of NP928. This drug-hydrogel combination has the potential to be rapidly developed into a therapeutic procedure that is amenable to general dental practice.
Topics: Dental Pulp; Dentin, Secondary; Dentinogenesis; Glycogen Synthase Kinase 3; Humans; Hydrogels; Thiadiazoles
PubMed: 34152872
DOI: 10.1177/00220345211020652 -
The Chinese Journal of Dental Research Mar 2024The dentine sialophosphoprotein (DSPP) gene is the only identified causative gene for dentinogenesis imperfecta type 2 (DGI-II), dentinogenesis imperfecta type 3... (Review)
Review
The dentine sialophosphoprotein (DSPP) gene is the only identified causative gene for dentinogenesis imperfecta type 2 (DGI-II), dentinogenesis imperfecta type 3 (DGI-III) and dentine dysplasia type 2 (DD-II). These three disorders may have similar molecular mechanisms involved in bridging the DSPP mutations and the resulting abnormal dentine mineralisation. The DSPP encoding proteins DSP (dentine sialoprotein) and DPP (dentine phosphoprotein) are positive regulators of dentine formation and perform a function during dentinogenesis. The present review focused on the recent findings and viewpoints regarding the relationship between DSPP and dentinogenesis as well as mineralisation from multiple perspectives, involving studies relating to spatial structure and tissue localisation of DSPP, DSP and DPP, the biochemical characteristics and biological function of these molecules, and the causative role of the proteins in phenotypes of the knockout mouse model and in hereditary dentine defects.
Topics: Animals; Mice; Calcification, Physiologic; Calcinosis; Dentin; Dentinogenesis Imperfecta; Disease Models, Animal; Mice, Knockout; Humans; Sialoglycoproteins; Phosphoproteins
PubMed: 38546516
DOI: 10.3290/j.cjdr.b5136791 -
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 -
Journal of Dental Research Jan 2020Bone sialoprotein (BSP) is a member of the SIBLING family with essential roles in skeletogenesis. In the developing teeth, although the expression and function of BSP in...
Bone sialoprotein (BSP) is a member of the SIBLING family with essential roles in skeletogenesis. In the developing teeth, although the expression and function of BSP in the formation of acellular cementum and periodontal attachment are well documented, there are uncertainties regarding the expression and function of BSP by odontoblasts and dentin. Reporter mice are valuable animal models for biological research, providing a gene expression readout that can contribute to cellular characterization within the context of a developmental process. In the present study, we examined the expression of a BSP-GFPtpz reporter mouse line during odontoblast differentiation, reparative dentinogenesis, and bone. In the developing teeth, BSP-GFPtpz was expressed at high levels in cementoblasts but not in odontoblasts or dentin. In bones, the transgene was highly expressed in osteoblasts at an early stage of differentiation. Interestingly, despite its lack of expression in odontoblasts and dental pulp during tooth development, the BSP-GFPtpz transgene was detected during in vitro mineralization of primary pulp cultures and during reparative dentinogenesis following pulp exposures. Importantly, under these experimental contexts, the expression of BSP-GFPtpz was still exclusive to DSPP-Cerulean, an odontoblast-specific reporter gene. This suggests that the combinatorial use of BSP-GFPtpz and DSPP-Cerulean can be a valuable experimental tool to distinguish osteogenic from dentinogenic cells, thereby providing an avenue to investigate mechanisms that distinctly regulate the lineage progression of progenitors into odontoblasts versus osteoblasts.
Topics: Animals; Cell Differentiation; Dental Pulp; Dentin, Secondary; Dentinogenesis; Gene Expression; Integrin-Binding Sialoprotein; Mice; Odontoblasts; Osteogenesis; Phosphoproteins; Sialoglycoproteins; Transgenes
PubMed: 31682548
DOI: 10.1177/0022034519885089