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Frontiers in Physiology 2023Mouse and human genetic studies indicate key roles of the ligand in odontogenesis. Previous studies have identified effectors and regulators of the Wnt signaling...
Mouse and human genetic studies indicate key roles of the ligand in odontogenesis. Previous studies have identified effectors and regulators of the Wnt signaling pathway actively expressed during key stages of tooth morphogenesis. However, limitations in multiplexing and spatial resolution hindered a more comprehensive analysis of these signaling molecules. Here, profiling of transcriptomes using fluorescent multiplex hybridization and single-cell RNA-sequencing (scRNA-seq) provide robust insight into the synchronized expression patterns of , , and simultaneously during tooth development. First, we identified transcripts restricted to the epithelium at the stage of tooth bud morphogenesis, contrasting that of and localization to the dental mesenchyme. By embryonic day 15.5 (E15.5), a marked shift of expression from dental epithelium to mesenchyme was noted, while and expression remained enriched in the mesenchyme. By postnatal day 0 (P0), co-localization patterns of , , and were observed in both terminally differentiating and secreting odontoblasts of molars and incisors. Interestingly, exhibited robust expression in fully differentiated ameloblasts at the developing cusp tip of both molars and incisors, an observation not previously noted in prior studies. At P7 and 14, after the mineralization of dentin and enamel, expression was limited to odontoblasts. Meanwhile, Wnt modulators showed reduced or absent signals in molars. In contrast, strong signals persisted in ameloblasts (for ) and odontoblasts (for , , and ) towards the proximal end of incisors, near the cervical loop. Our scRNA-seq analysis used CellChat to further contextualize Wnt pathway-mediated communication between cells by examining ligand-receptor interactions among different clusters. The co-localization pattern of , , and in both terminally differentiating and secreting odontoblasts of molars and incisors potentially signifies the crucial ligand-modulator interaction along the gradient of cytodifferentiation starting from each cusp tip towards the apical region. These data provide cell type-specific insight into the role of Wnt ligands and mediators during epithelial-mesenchymal interactions in odontogenesis.
PubMed: 38274045
DOI: 10.3389/fphys.2023.1316635 -
Frontiers in Physiology 2023Upon endoplasmic reticulum (ER) stress, inositol-requiring enzyme 1 (IRE1) is activated, which subsequently converts an unspliced X-box binding protein 1 () mRNA to a...
Upon endoplasmic reticulum (ER) stress, inositol-requiring enzyme 1 (IRE1) is activated, which subsequently converts an unspliced X-box binding protein 1 () mRNA to a spliced mRNA that encodes a potent XBP1S transcription factor. XBP1S is essential for relieving ER stress and secretory cell differentiation. We previously established ; mice that constitutively expressed XBP1S in the -expressing cells as well as in the cells derived from the -expressing cells. In this study, we analyzed the dental phenotype of ; mice. We first generated a mutant minigene that corresponds to the recombinant allele (the allele that has undergone Cre-mediated recombination) and confirmed that the minigene expressed XBP1S that does not require IRE1α activation . Consistently, immunohistochemistry showed that XBP1S was constitutively expressed in the odontoblasts and other dental pulp cells in ; mice. Plain X-ray radiography and µCT analysis revealed that constitutive expression of XBP1S altered the dental pulp chamber roof- and floor-dentin formation, resulting in a significant reduction in dentin/cementum formation in ; mice, compared to age-matched control mice. However, there is no significant difference in the density of dentin/cementum between these two groups of mice. Histologically, persistent expression of XBP1S caused a morphological change in odontoblasts in ; mice. Nevertheless, hybridization and immunohistochemistry analyses showed that continuous expression of XBP1S had no apparent effects on the expression of the and genes. In conclusion, these results support that sustained production of XBP1S adversely affected odontoblast function and dentin formation.
PubMed: 38274041
DOI: 10.3389/fphys.2023.1319954 -
International Journal of Molecular... Jan 2024MMP13 gene expression increases up to 2000-fold in mineralizing dental pulp cells (DPCs), with research previously demonstrating that global MMP13 deletion resulted in...
MMP13 gene expression increases up to 2000-fold in mineralizing dental pulp cells (DPCs), with research previously demonstrating that global MMP13 deletion resulted in critical alterations in the dentine phenotype, affecting dentine-tubule regularity, the odontoblast palisade, and significantly reducing the dentine volume. Global MMP13-KO and wild-type mice of a range of ages had their molar teeth injured to stimulate reactionary tertiary dentinogenesis. The response was measured qualitatively and quantitatively using histology, immunohistochemistry, micro-CT, and qRT-PCR in order to assess changes in the nature and volume of dentine deposited as well as mechanistic links. MMP13 loss affected the reactionary tertiary dentine quality and volume after cuspal injury and reduced Nestin expression in a non-exposure injury model, as well as mechanistic links between MMP13 and the Wnt-responsive gene Axin2. Acute pulpal injury and pulp exposure to oral fluids in mice teeth showed upregulation of the MMP13 in vivo, with an increase in the gene expression of , , and evident. These results indicate that MMP13 is involved in tertiary reactionary dentine formation after tooth injury in vivo, potentially acting as a key molecule in the dental pulp during dentine-pulp repair processes.
Topics: Animals; Mice; Dentinogenesis; Matrix Metalloproteinase 13; Molar; Odontoblasts; Tooth Injuries
PubMed: 38255947
DOI: 10.3390/ijms25020875 -
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 -
Dental Abnormalities in Two Dental-Skeletal-Retinal Anomaly-Positive Cane Corso Dogs: A Case Series.Journal of Veterinary Dentistry Dec 2023Dental-skeletal-retinal-anomaly (DSRA) is a newly described collagenopathy in Cane Corso dogs. The causative mutation has been linked with splice defects within the...
Dental-skeletal-retinal-anomaly (DSRA) is a newly described collagenopathy in Cane Corso dogs. The causative mutation has been linked with splice defects within the melanoma inhibitory activity member 3 (MIA/3) gene that codes for the TANGO1 protein. This case series presents the first dental-related radiographic and histopathological abnormalities in two dogs with genetically confirmed DSRA. The clinical, radiological, and histological features are similar to those reported for MIA3/TANGO1 splice defects previously reported in humans and knockout mice. Common clinical features of these patients include generalized opalescent discoloration of the permanent dentition (intrinsic dyschromia), enamel defects, fractured teeth, vision loss, shortened physical stature, and orthopedic abnormalities that resulted in chronic, early-onset lameness. Intraoral radiography revealed delayed dentin deposition, evidence of endodontic disease, and dental hard tissue loss in both cases. Histopathologic findings for both cases were consistent with dentinogenesis imperfecta (DGI). DSRA exhibits autosomal recessive heritability and commercial diagnostic tests are now available. Clinicians should be aware of the etiopathogenesis, genetic inheritance and associated comorbidities in order to treat and counsel clients on the management of this condition. It is recommended that all breeding individuals be tested, and carriers be sterilized or omitted from the breeding population. This case study describes intraoral diagnoses, treatments, and follow-up of two DSRA-positive dogs.
PubMed: 38146186
DOI: 10.1177/08987564231215170 -
Puerto Rico Health Sciences Journal Dec 2023Mucopolysaccharidosis (MPS) is a metabolic disorder resulting from a deficiency of lysosomal enzymes. It is an autosomal recessive disorder with similar incidences in... (Review)
Review
Mucopolysaccharidosis (MPS) is a metabolic disorder resulting from a deficiency of lysosomal enzymes. It is an autosomal recessive disorder with similar incidences in men and women. Mucopolysaccharidosis type IV A is caused by a deficiency of N-acetylgalactosamine-6-sulfatase, which deficiency is, in turn, caused by alterations in the GALNS gene. It is marked by a short stature, a pigeon chest, frontal bossing, kyphosis, and a flat nasal bridge. Intraorally, macroglossia, hypodontia, dentinogenesis imperfecta, a broad mouth, and an anterior open bite are some of the common features. The present paper reports on a case of MPS in a 5-year-old male patient, along with providing a review of the literature and insight into the oral manifestations related to MPS IV A, also called Morquio A syndrome, and its dental treatment. It aims to highlight the clinical recommendations for oral health care in such cases during different phases of MPS IV A treatment.
Topics: Male; Humans; Child; Female; Child, Preschool; Mucopolysaccharidosis IV; Chondroitinsulfatases; Delivery of Health Care
PubMed: 38104293
DOI: No ID Found