-
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 -
Case Reports in Dentistry 2024Pulp involvement of immature permanent teeth with dentinogenesis imperfecta is challenging and could lead to extraction. A case of dentinogenesis imperfecta-induced...
Pulp involvement of immature permanent teeth with dentinogenesis imperfecta is challenging and could lead to extraction. A case of dentinogenesis imperfecta-induced periapical periodontitis of an immature permanent tooth was treated with regenerative endodontic treatment (RET), and root maturation was observed in 12-month follow-up. An 8-year-old girl presented acute pain and swelling in central mandibular region. Clinical and radiographic examination revealed "shell teeth" appearance of teeth 31, 41, and 42. Periapical lesion of tooth 31 was observed. Tooth 41 was previously treated with apexification. RET was planned and carried out for the necrotic tooth (tooth 31) with dentinogenesis imperfecta. The 1-, 3-, 7-, and 12-month postoperative recall revealed complete healing of periapical lesions. Root maturation characterized by elongation of root, thickening of dentinal walls, and closure of root apex was observed with radiographic examinations. We show that RET could be a desirable treatment for necrotic immature permanent teeth with dentinogenesis imperfecta and lead to resolution of endodontic lesions as well as maturation of dental root. The findings of this case suggest that RET should be considered by endodontist and pediatric dentist to treat teeth with similar dental anomalies and apical periodontitis.
PubMed: 38223911
DOI: 10.1155/2024/5128588 -
The Saudi Dental Journal Dec 2023Dental caries (DC)-induced pulp infections usually undergo the common endodontic treatment, root canal therapy (RCT). Endodontically treated teeth are devitalized,...
Dental caries (DC)-induced pulp infections usually undergo the common endodontic treatment, root canal therapy (RCT). Endodontically treated teeth are devitalized, become brittle and susceptible for re-infection which eventually results in dental loss. These complications arise because the devitalized pulp losses its ability for innate homeostasis, repair and regeneration. Therefore, restoring the vitality, structure and function of the inflamed pulp and compromised dentin have become the focal points in regenerative endodontics. There are very few evidences, so far, that connect methylenetetrahydrofolate reductase single nucleotide polymorphisms (MTHFR-SNPs) and dental disorders. However, the primary consequences of MTHFR-SNPs, in terms of excessive homocysteine and folate deficiency, are well-known contributors to dental diseases. This article identifies the possible mechanisms by which MTHFR-SNP-carriers are susceptible for DC-induced pulp inflammation (PI); and discusses a cell-homing based strategy for transplantation in an orthotopic model to regenerate the functional dentine-pulp complex which includes dentinogenesis, neurogenesis and vasculogenesis, in the SNP-carriers.
PubMed: 38170041
DOI: 10.1016/j.sdentj.2023.08.008 -
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 -
The American Journal of Case Reports Dec 2023BACKGROUND Osteogenesis imperfecta (OI) is a rare genetic disease that results from mutations in type 1 collagen (COL1) or its interacting proteins. Such mutations lead...
BACKGROUND Osteogenesis imperfecta (OI) is a rare genetic disease that results from mutations in type 1 collagen (COL1) or its interacting proteins. Such mutations lead to defects in bone structure, causing brittle bones, short stature, hearing loss, and dental problems, among others. The current classification system arranges OI into types according to a clinical phenotype that includes the severity of the disease and a combination of specific features, such as blue sclerae and dental abnormalities. CASE REPORT Here, we present a clinical report of a 3-year-old boy diagnosed with OI in utero who has been followed by our pediatric clinic postnatally. The patient was born with multiple bone fractures, a small head circumference, and blue sclerae and later had a concomitant diagnosis of dentinogenesis imperfecta (DI). Soon after birth, the patient was started on bisphosphonate and calcium/vitamin D treatment. The patient's OI type was inconclusive due to the dramatic difference between perinatal and postnatal phenotypes, the presence of blue sclerae, and the additional diagnosis of DI. The patient experienced only 1 new bone fracture postnatally, had normal anthropometric measurements except for short stature, and was healthy. CONCLUSIONS This clinical case is unique owing to the dramatic perinatal and mild postnatal OI phenotypes. This and the unique combination of postnatal features demonstrate that classical OI typing could be inconclusive in atypical disease presentation. This case may demonstrate a new classification possibility outside the current OI nomenclature. However, the potential beneficial role of pharmacological treatment in the clinical outcome of OI cannot be excluded.
Topics: Male; Child; Humans; Child, Preschool; Collagen Type I; Osteogenesis Imperfecta; Mutation; Phenotype
PubMed: 38148598
DOI: 10.12659/AJCR.942239 -
Journal of Functional Biomaterials Nov 2023In recent years, alternative pulpal therapies targeting dentinogenesis signaling pathways using different peptides have been investigated. The aim of this study was to...
UNLABELLED
In recent years, alternative pulpal therapies targeting dentinogenesis signaling pathways using different peptides have been investigated. The aim of this study was to verify the effectiveness of poly(aspartic acid), pAsp, in dentin regeneration using an animal model.
METHODS
Mechanical pulp exposure was performed in the upper molars of 56 Wistar rats, randomly divided as follows (n = 14): control (no treatment); MTA group-pulp capping with mineral trioxide aggregate (MTA Angelus); pAsp group-application of 20 μL of pAsp solution (25 mg·mL); MTA+pAsp group-application of MTA mixed with pAsp (5:1 by mass). Animals were euthanized after 7 or 21 days. Histological sections were submitted to hematoxylin-eosin and Brown and Brenn staining and immunohistochemical analysis for osteopontin (OPN) and dentin matrix protein 1 (DMP 1).
RESULTS
At 7 days, an acute inflammatory infiltrate and the presence of disorganized mineralized tissue were observed in all groups. At 21 days, the quality and thickness of the reparative dentin in treated groups were superior to the control, and bacterial contamination was observed in two MTA-pAsp specimens. While all treated groups showed intense immunostaining for OPN at 21 days, only the pAsp group expressed DMP 1, indicating the presence of fully differentiated odontoblast-like cells.
CONCLUSION
Poly(aspartic) acid promoted dentin regeneration in rat molars in the absence of an additional calcium source and may be an alternative to MTA as a pulp-capping agent.
PubMed: 37998106
DOI: 10.3390/jfb14110537 -
Frontiers in Cell and Developmental... 2023Heparan sulfate proteoglycans (HSPGs) surround the surface of odontoblasts, and their modification affects their affinity for Wnt ligands. This study proposes applying...
On-demand chlorine dioxide solution enhances odontoblast differentiation through desulfation of cell surface heparan sulfate proteoglycan and subsequent activation of canonical Wnt signaling.
Heparan sulfate proteoglycans (HSPGs) surround the surface of odontoblasts, and their modification affects their affinity for Wnt ligands. This study proposes applying Matching Transformation System (MA-T), a novel chlorinated oxidant, to enhance dentinogenesis. MA-T treatment in odontoblasts decreased sulfation of HSPG and upregulated the expression of () and () via activation of canonical Wnt signaling . application of MA-T also enhanced dentin matrix formation in developing tooth explants. Reanalysis of a public single-cell RNA-seq dataset revealed significant Wnt activity in the odontoblast population, with enrichment for and . Silencing assays showed that and were redundant in inducing and mRNA expression. These Wnt ligands' expression was upregulated by MA-T treatment, and TCF/LEF binding sites are present in their promoters. Furthermore, the Wnt inhibitors Notum and Dkk1 were enriched in odontoblasts, and their expression was also upregulated by MA-T treatment, together suggesting autonomous maintenance of Wnt signaling in odontoblasts. This study provides evidence that MA-T activates dentinogenesis by modifying HSPG and through subsequent activation of Wnt signaling.
PubMed: 37954207
DOI: 10.3389/fcell.2023.1271455 -
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 -
Acta Stomatologica Croatica Sep 2023The aim of this study was to determine the average dentin wall thickness (DWT) of the maxillary central incisor (MCI) required for performing finite element analysis...
OBJECTIVE
The aim of this study was to determine the average dentin wall thickness (DWT) of the maxillary central incisor (MCI) required for performing finite element analysis (FEA) models of root development.
MATERIAL AND METHODS
A total of 137 intraoral periapical radiographs of MCI in children aged 7 to 11 years were examined and then classified into 5 groups according to root development stages, which included 1/2 of root development (S1), 3/4 of root development (S2), more than 3/4 of root development (S3), complete development with wide-open apex (S4) and complete development with closed apex (S5). DWT was measured at three reference (horizontal) lines: at a distance of 1 mm from the apex (M), 4 mm from the apex (L) and at the cervical line (K). The distal dentin wall thickness (M1, L1, and K1), the pulp thickness (M2, L2, and K2), the mesial dentin wall thickness (M3, L3, and K3), and the apex thickness (N) were measured using the diagnostic software Soredex Scanora 5.1.2.4. Statistical analysis compared the values of the parameters K, L, and M between developmental stages (multivariate ANOVA) and the linear correlations between the parameters (Pearson's correlation analysis). All analyses were performed at significance level α = 0.05.
RESULTS
There were statistically significant differences between the developmental stages for parameters L and M, while no significant differences were found for parameter K. Most of the correlations between the parameters were statistically significant, with the values of the Pearson correlation coefficient R > 0.6 considered practically significant. All parameters on the same reference line for distal and mesial dentin wall thickness and for pulp thickness correlated well with each other (R = 0.46 - 0.68), but there was no statistically significant correlation with total root thickness on the same reference line (parameters K, L, or M), except for parameter K3 (R = 0.42).
CONCLUSION
Despite the limitations of this study, the mean values of the selected parameters for the 5 groups of developmental stages of the maxillary central incisor could be used to model dentin wall thickness using finite element analysis.
PubMed: 37808407
DOI: 10.15644/asc57/3/1 -
Research Square Sep 2023BMP2 signaling plays a pivotal role in odontoblast differentiation and maturation during odontogenesis. Teeth lacking Bmp2 exhibit a morphology reminiscent of...
BMP2 signaling plays a pivotal role in odontoblast differentiation and maturation during odontogenesis. Teeth lacking Bmp2 exhibit a morphology reminiscent of dentinogenesis imperfecta (DGI), associated with mutations in dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP) genes. Mechanisms by which BMP2 signaling influences expressions of DSPP and DMP1 and contributes to DGI remain elusive. To study the roles of BMP2 in dentin development, we generated Bmp2 conditional knockout (cKO) mice. Through a comprehensive approach involving RNA-seq, immunohistochemistry, promoter activity, ChIP, and Re-ChIP, we investigated downstream targets of Bmp2. Notably, the absence of Bmp2 in cKO mice led to dentin insufficiency akin to DGI. Disrupted Bmp2 signaling was linked to decreased expression of Dspp and Dmp1, as well as alterations in intracellular translocation of transcription factors Dlx3 and Sp7. Intriguingly, upregulation of Dlx3, Dmp1, Dspp, and Sp7, driven by BMP2, fostered differentiation of dental mesenchymal cells and biomineralization. Mechanistically, BMP2 induced phosphorylation of Dlx3, Sp7, and histone acetyltransferase GCN5 at Thr and Tyr residues, mediated by Akt and Erk kinases. This phosphorylation facilitated protein nuclear translocation, promoting interactions between Sp7 and Dlx3, as well as with GCN5 on Dspp and Dmp1 promoters. The synergy between Dlx3 and Sp7 bolstered transcription of Dspp and Dmp1. Notably, BMP2-driven GCN5 acetylated Sp7 and histone H3, while also recruiting RNA polymerase II to Dmp1 and Dspp chromatins, enhancing their transcriptions. Intriguingly, BMP2 suppressed the expression of histone deacetylases. we unveil hitherto uncharted involvement of BMP2 in dental cell differentiation and dentine development through pAkt/pErk42/44/Dlx3/Sp7/GCN5/Dspp/Dmp1.
PubMed: 37790473
DOI: 10.21203/rs.3.rs-3299295/v1