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International Journal of Oral Science Mar 2024Human with bi-allelic WNT10A mutations and epithelial Wnt10a knockout mice present enlarged pulp chamber and apical displacement of the root furcation of multi-rooted...
Human with bi-allelic WNT10A mutations and epithelial Wnt10a knockout mice present enlarged pulp chamber and apical displacement of the root furcation of multi-rooted teeth, known as taurodontism; thus, indicating the critical role of Wnt10a in tooth root morphogenesis. However, the endogenous mechanism by which epithelial Wnt10a regulates Hertwig's epithelial root sheath (HERS) cellular behaviors and contributes to root furcation patterning remains unclear. In this study, we found that HERS in the presumptive root furcating region failed to elongate at an appropriate horizontal level in K14-Cre;Wnt10a mice from post-natal day 0.5 (PN0.5) to PN4.5. EdU assays and immunofluorescent staining of cyclin D1 revealed significantly decreased proliferation activity of inner enamel epithelial (IEE) cells of HERS in K14-Cre;Wnt10a mice at PN2.5 and PN3.5. Immunofluorescent staining of E-Cadherin and acetyl-α-Tubulin demonstrated that the IEE cells of HERS tended to divide perpendicularly to the horizontal plane, which impaired the horizontal extension of HERS in the presumptive root furcating region of K14-Cre;Wnt10a mice. RNA-seq and immunofluorescence showed that the expressions of Jag1 and Notch2 were downregulated in IEE cells of HERS in K14-Cre;Wnt10a mice. Furthermore, after activation of Notch signaling in K14-Cre;Wnt10a molars by Notch2 adenovirus and kidney capsule grafts, the root furcation defect was partially rescued. Taken together, our study demonstrates that an epithelial Wnt10a-Notch signaling axis is crucial for modulating HERS cell proper proliferation and horizontal-oriented division during tooth root furcation morphogenesis.
Topics: Humans; Female; Mice; Animals; Tooth Root; Tooth; Odontogenesis; Signal Transduction; Dental Enamel; Epithelial Cells; Nerve Tissue Proteins; Wnt Proteins
PubMed: 38480698
DOI: 10.1038/s41368-024-00288-x -
Proceedings of the National Academy of... Mar 2024According to Dollo's Law of irreversibility in evolution, a lost structure is usually considered to be unable to reappear in evolution due to the accumulation over time...
According to Dollo's Law of irreversibility in evolution, a lost structure is usually considered to be unable to reappear in evolution due to the accumulation over time of mutations in the genes required for its formation. Cypriniform fish are a classic model of evolutionary loss because, while they form fully operational teeth in the ventral posterior pharynx, unlike other teleosts, they do not possess oral teeth. Paleontological data show that Cypriniforms, a clade of teleost fish that includes the zebrafish, lost their oral teeth 50 to 100 Mya. In order to attempt to reverse oral tooth loss in zebrafish, we block the degradation of endogenous levels of retinoic acid (RA) using a specific inhibitor of the Cyp26 RA degrading enzymes. We demonstrate the inhibition of endogenous RA degradation is sufficient to restore oral tooth induction as marked by the re-appearance of expression of early dental mesenchyme and epithelium genes such as and in the oral cavity. Furthermore, we show that these exogenously induced oral tooth germs are able to be at least partly calcified. Taken together, our data show that modifications of signaling pathways can have a significant effect on the reemergence of once-lost structures leading to experimentally induced reversibility of evolutionary tooth loss in cypriniforms.
Topics: Animals; Zebrafish; Tooth Loss; Odontogenesis; Perciformes
PubMed: 38446853
DOI: 10.1073/pnas.2321162121 -
Glycobiology Apr 2024This review delves into the roles of glycosaminoglycans (GAGs), integral components of proteoglycans, in tooth development. Proteoglycans consist of a core protein... (Review)
Review
This review delves into the roles of glycosaminoglycans (GAGs), integral components of proteoglycans, in tooth development. Proteoglycans consist of a core protein linked to GAG chains, comprised of repeating disaccharide units. GAGs are classified into several types, such as hyaluronic acid, heparan sulfate, chondroitin sulfate, dermatan sulfate, and keratan sulfate. Functioning as critical macromolecular components within the dental basement membrane, these GAGs facilitate cell adhesion and aggregation, and play key roles in regulating cell proliferation and differentiation, thereby significantly influencing tooth morphogenesis. Notably, our recent research has identified the hyaluronan-degrading enzyme Transmembrane protein 2 (Tmem2) and we have conducted functional analyses using mouse models. These studies have unveiled the essential role of Tmem2-mediated hyaluronan degradation and its involvement in hyaluronan-mediated cell adhesion during tooth formation. This review provides a comprehensive summary of the current understanding of GAG functions in tooth development, integrating insights from recent research, and discusses future directions in this field.
Topics: Mice; Animals; Glycosaminoglycans; Hyaluronic Acid; Proteoglycans; Keratan Sulfate; Chondroitin Sulfates; Heparitin Sulfate; Odontogenesis; Dermatan Sulfate
PubMed: 38438145
DOI: 10.1093/glycob/cwae024 -
International Dental Journal Jun 2024This study aimed to investigate the in vitro effects of root canal filling and repair paste (nRoot BP) on human dental pulp stem cells (hDPSCs).
OBJECTIVES
This study aimed to investigate the in vitro effects of root canal filling and repair paste (nRoot BP) on human dental pulp stem cells (hDPSCs).
METHODS
The effects of nRoot BP and iRoot BP Plus on the adhesion, proliferation, migration, and differentiation of hDPSCs were examined in vitro for 72 hours. The adhesion of cells was observed using immunofluorescence rhodamine ghost pen cyclic peptide staining and scanning electron microscopy (SEM). Cell density and changes in migration area were measured under a fluorescence inverted microscope. Fluorescent quantitative PCR was performed to detect genes related to odontogenesis and osteogenesis.
RESULTS
Cells adhering to the surfaces of nRoot BP and iRoot BP Plus exhibited similar irregular polygonal morphologies, with cells extending irregular pseudopods to adhere to the materials. CCK-8 results indicated that the density of living cells for nRoot BP and iRoot BP Plus was lower than that of the blank control group at 3 and 5 days of culture. There was no significant difference in cell migration between the groups (P > .05). The migration ability of iRoot BP Plus and nRoot BP was similar to that of the control group. Both nRoot BP and iRoot BP Plus increased the expression of the RUNX2 gene, but there was no significant difference between the groups (P < .05). Furthermore, both nRoot BP and iRoot BP Plus downregulated the expression of the DSPP gene, with no significant difference between them (P > .05).
CONCLUSIONS
nRoot BP exhibited a slight inhibition of hDPSC proliferation but did not affect the adhesion and migration of hDPSCs. The impact of nRoot BP on the osteogenic and odontogenic differentiation of hDPSCs was similar to that of iRoot BP Plus.
Topics: Humans; Dental Pulp; Stem Cells; Cell Proliferation; Cell Movement; Cell Differentiation; Cell Adhesion; Root Canal Filling Materials; Ceramics; Nanoparticles; Osteogenesis; Microscopy, Electron, Scanning; Cells, Cultured; Drug Combinations; Core Binding Factor Alpha 1 Subunit; In Vitro Techniques; Odontogenesis; Biocompatible Materials; Silicates
PubMed: 38431469
DOI: 10.1016/j.identj.2023.12.008 -
Biomedicines Feb 2024Exosomes derived from M2 macrophages (M2-Exos) exhibit tremendous potential for inducing tissue repair and regeneration. Herein, this study was designed to elucidate the...
Multifunctional Exosomes Derived from M2 Macrophages with Enhanced Odontogenesis, Neurogenesis and Angiogenesis for Regenerative Endodontic Therapy: An In Vitro and In Vivo Investigation.
INTRODUCTION
Exosomes derived from M2 macrophages (M2-Exos) exhibit tremendous potential for inducing tissue repair and regeneration. Herein, this study was designed to elucidate the biological roles of M2-Exos in regenerative endodontic therapy (RET) compared with exosomes from M1 macrophages (M1-Exos).
METHODS
The internalization of M1-Exos and M2-Exos by dental pulp stem cells (DPSCs) and human umbilical vein endothelial cells (HUVECs) was detected by uptake assay. The effects of M1-Exos and M2-Exos on DPSC and HUVEC behaviors, including migration, proliferation, odonto/osteogenesis, neurogenesis, and angiogenesis were determined in vitro. Then, Matrigel plugs incorporating M2-Exos were transplanted subcutaneously into nude mice. Immunostaining for vascular endothelial growth factor (VEGF) and CD31 was performed to validate capillary-like networks.
RESULTS
M1-Exos and M2-Exos were effectively absorbed by DPSCs and HUVECs. Compared with M1-Exos, M2-Exos considerably facilitated the proliferation and migration of DPSCs and HUVECs. Furthermore, M2-Exos robustly promoted ALP activity, mineral nodule deposition, and the odonto/osteogenic marker expression of DPSCs, indicating the powerful odonto/osteogenic potential of M2-Exos. In sharp contrast with M1-Exos, which inhibited the neurogenic capacity of DPSCs, M2-Exos contributed to a significantly augmented expression of neurogenic genes and the stronger immunostaining of Nestin. Consistent with remarkably enhanced angiogenic markers and tubular structure formation in DPSCs and HUVECs in vitro, the employment of M2-Exos gave rise to more abundant vascular networks, dramatically higher VEGF expression, and widely spread CD31 tubular lumens in vivo, supporting the enormous pro-angiogenic capability of M2-Exos.
CONCLUSIONS
The multifaceted roles of M2-Exos in ameliorating DPSC and HUVEC functions potentially contribute to complete functional pulp-dentin complex regeneration.
PubMed: 38398043
DOI: 10.3390/biomedicines12020441 -
Materials Today. Bio Apr 2024Human-treated dentin matrix (hTDM) has recently been studied as a natural extracellular matrix-based biomaterial for dentin pulp regeneration. However, porcine-treated...
BACKGROUND
Human-treated dentin matrix (hTDM) has recently been studied as a natural extracellular matrix-based biomaterial for dentin pulp regeneration. However, porcine-treated dentin matrix (pTDM) is a potential alternative scaffold due to limited availability. However, there is a dearth of information regarding the protein composition and underlying molecular mechanisms of pTDM.Methods: hTDM and pTDM were fabricated using human and porcine teeth, respectively, and their morphological characteristics were examined using scanning electron microscopy. Stem cells derived from human exfoliated deciduous teeth (SHEDs) were isolated and characterized using flow cytometry and multilineage differentiation assays. SHEDs were cultured in three-dimensional environments with hTDM, pTDM, or biphasic hydroxyapatite/tricalcium phosphate. The expression of odontogenesis markers in SHEDs were assessed using real-time polymerase chain reaction and immunochemical staining. Subsequently, SHEDs/TDM and SHEDs/HA/TCP complexes were transplanted subcutaneously into nude mice. The protein composition of pTDM was analyzed using proteomics and compared to previously published data on hTDM.Results: pTDM and hTDM elicited comparable upregulation of odontogenesis-related genes and proteins in SHEDs. Furthermore, both demonstrated the capacity to stimulate root-related tissue regeneration . Proteomic analysis revealed the presence of 278 protein groups in pTDM, with collagens being the most abundant. Additionally, pTDM and hTDM shared 58 identical proteins, which may contribute to their similar abilities to induce odontogenesis.
CONCLUSIONS
Both hTDM and pTDM exhibit comparable capabilities in inducing odontogenesis, potentially owing to their distinctive bioactive molecular networks.
PubMed: 38371466
DOI: 10.1016/j.mtbio.2024.100990 -
Journal of Oral and Maxillofacial... 2023Cell adhesion molecules (CAMs) are found on the surface of all cells, where they allow dynamic processes to take place. These include cadherins, integrins, selectins and... (Review)
Review
BACKGROUND
Cell adhesion molecules (CAMs) are found on the surface of all cells, where they allow dynamic processes to take place. These include cadherins, integrins, selectins and Immunoglobulin superfamily. Directly associated with β-integrin tails is a multidomain protein known as paxillin. However, CAMs participate in cell-cell and extracellular matrix-cell interactions during histomorphogenesis in the various phases of odontogenesis. Some tumours or cysts like ameloblastoma (AB) or odontogenic keratocyst (OKC) having odontogenic origin show disturbance in the interaction of these CAMs. Hence, the assessment of paxillin expression in AB and OKC was carried out.
MATERIALS AND METHODS
The present observational study comprised 30 clinically and histologically confirmed cases of AB and OKC. All the slides were stained immunohistochemically using a paxillin antibody.
RESULTS
Upon comparison of staining intensity of paxillin among AB and OKC showed statistically significant result, whereas quantitative staining and final summation showed non-significant result. Gender-wise comparison of paxillin staining intensity, quantitative staining and final summation among OKC showed significant result; however, in AB, staining intensity showed non-significant result, whereas quantitative staining and final summation showed significant result.
CONCLUSION
Paxillin has the greatest influence on tissue morphogenesis and development. The regulation of cell mobility is aided by the multiple roles that paxillin plays in a range of cells and tissues. However, further studies using a large sample size, along with other molecular analytical methods, may be essential to draw a definite conclusion about the association of paxillin and its exact function in OKC and AB.
PubMed: 38304525
DOI: 10.4103/jomfp.jomfp_312_23 -
International Journal of Oral Science Feb 2024Odontogenic maxillary sinusitis (OMS) is a subtype of maxillary sinusitis (MS). It is actually inflammation of the maxillary sinus that secondary to adjacent infectious... (Review)
Review
Odontogenic maxillary sinusitis (OMS) is a subtype of maxillary sinusitis (MS). It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion. Due to the lack of unique clinical features, OMS is difficult to distinguish from other types of rhinosinusitis. Besides, the characteristic infectious pathogeny of OMS makes it is resistant to conventional therapies of rhinosinusitis. Its current diagnosis and treatment are thus facing great difficulties. The multi-disciplinary cooperation between otolaryngologists and dentists is absolutely urgent to settle these questions and to acquire standardized diagnostic and treatment regimen for OMS. However, this disease has actually received little attention and has been underrepresented by relatively low publication volume and quality. Based on systematically reviewed literature and practical experiences of expert members, our consensus focuses on characteristics, symptoms, classification and diagnosis of OMS, and further put forward multi-disciplinary treatment decisions for OMS, as well as the common treatment complications and relative managements. This consensus aims to increase attention to OMS, and optimize the clinical diagnosis and decision-making of OMS, which finally provides evidence-based options for OMS clinical management.
Topics: Humans; Maxillary Sinusitis; Consensus; Maxillary Sinus; Odontogenesis; Rhinosinusitis
PubMed: 38302479
DOI: 10.1038/s41368-024-00278-z -
Scientific Reports Jan 2024The classification and localization of odontogenic lesions from panoramic radiographs is a challenging task due to the positional biases and class imbalances of the...
The classification and localization of odontogenic lesions from panoramic radiographs is a challenging task due to the positional biases and class imbalances of the lesions. To address these challenges, a novel neural network, DOLNet, is proposed that uses mutually influencing hierarchical attention across different image scales to jointly learn the global representation of the entire jaw and the local discrepancy between normal tissue and lesions. The proposed approach uses local attention to learn representations within a patch. From the patch-level representations, we generate inter-patch, i.e., global, attention maps to represent the positional prior of lesions in the whole image. Global attention enables the reciprocal calibration of path-level representations by considering non-local information from other patches, thereby improving the generation of whole-image-level representation. To address class imbalances, we propose an effective data augmentation technique that involves merging lesion crops with normal images, thereby synthesizing new abnormal cases for effective model training. Our approach outperforms recent studies, enhancing the classification performance by up to 42.4% and 44.2% in recall and F1 scores, respectively, and ensuring robust lesion localization with respect to lesion size variations and positional biases. Our approach further outperforms human expert clinicians in classification by 10.7 % and 10.8 % in recall and F1 score, respectively.
Topics: Humans; Deep Learning; Neural Networks, Computer; Radiography, Panoramic; Odontogenesis
PubMed: 38291068
DOI: 10.1038/s41598-024-52929-0 -
Cureus Dec 2023Dental fluorosis is a developmental disturbance of dental enamels, caused by successive exposures to high concentrations of fluoride during odontogenesis, leading to...
Prevalence and Distribution of Developmental Defects of Enamel in Children Aged 12-15 Years in Fazilka District, Punjab, India, and Their Correlation With Drinking Water Fluoride Level.
BACKGROUND AND OBJECTIVES
Dental fluorosis is a developmental disturbance of dental enamels, caused by successive exposures to high concentrations of fluoride during odontogenesis, leading to enamels with lower mineral content and increased porosity. The objective of the present study was to assess the prevalence and severity of developmental defects and their relationship to fluoride levels in drinking water. Methods: Ten villages were selected from Fazilka district, Punjab, India. A total of 1000 (519 males, 481 females) school children aged 12-15 years formed the study population. Eutech ION 2700 (Thermo Fisher Scientific, Waltham, Massachusetts, United States) was used for the estimation of fluoride levels in water. Developmental defects were screened and assessed using the modified Developmental Defects of Enamel (DDE) Index. Statistical evaluation was done using Karl Pearson's coefficient of correlation and the Chi-square test with IBM SPSS Statistics for Windows, Version 23, (Released 2015; IBM Corp., Armonk, New York, United States).
RESULTS
The fluoride concentration in drinking water ranged from 0.5 to 2.0 ppm. The prevalence of developmental defects among the study population was 73.4% (range 59% to 100%). The most commonly observed type of defect was diffuse opacity (score 4) in 22.8% of the children. The premolars were the most commonly affected teeth. There was a significant positive correlation between the type (r=0.95; p<0.001) and extent (r=0.82; p<0.001) of developmental defects to the fluoride levels in drinking water. Conclusion: The drinking water from about 50% of the villages had fluoride levels of 1 ppm or >1 ppm. A significant positive correlation between the severity of enamel defects and increased fluoride levels in water was deciphered. Thus, a simple, effective, and inexpensive method of de-fluoridation of drinking water should be prioritized if alternative sources of drinking water are not made available.
PubMed: 38288183
DOI: 10.7759/cureus.51238