-
Journal of Molecular Histology Apr 2024Cytodifferentiation of odontogenic cells, a late stage event in odontogenesis is based on gene regulation. However, studies on the identification of the involved genes... (Review)
Review
Cytodifferentiation of odontogenic cells, a late stage event in odontogenesis is based on gene regulation. However, studies on the identification of the involved genes are scarce. The present study aimed to search for molecules for the cytodifferentiation of ameloblastic cells in rats. Differential display-PCR revealed a differentially expressed gene between cap/early bell stage and hard tissue formation stage in molars. This gene was identified as N-myc Downregulated Gene 1 (Ndrg1), which is the first report in tooth development. Real time PCR and western blotting confirmed that the mRNA level of Ndrg1 was higher during enamel formation than the cap stage. Ndrg1 expression was upregulated in the early bell, crown, and root stages in a time-dependent manner. These patterns of expression were similar in Ndrg2, but Ndrg3 and Ndrg4 levels did not change during the developmental stages. Immunofluorescence revealed that strong immunoreactivity against Ndrg1 were detected in differentiated ameloblasts only, not inner enamel epithelium, odontoblasts and ameloblastic cells in defected enamel regions. Alkaline phosphatase and alizarin red s stains along with real time PCR, revealed that Ndrg1 and Ndrg2 were involved in cytodifferentiation and enamel matrix mineralization by selectively regulating amelogenin and ameloblastin genes in SF2 ameloblastic cells. These results suggest that Ndrg may play a crucial functional role in the cytodifferentiation of ameloblasts for amelogenesis.
Topics: Animals; Rats; Ameloblasts; Amelogenesis; Molar; Muscle Proteins; Nerve Tissue Proteins; Odontogenesis; Proteins
PubMed: 38407765
DOI: 10.1007/s10735-024-10182-9 -
Journal of Dental Research Apr 2024Tooth development and regeneration are regulated through a complex signaling network. Previous studies have focused on the exploration of intracellular signaling... (Review)
Review
Tooth development and regeneration are regulated through a complex signaling network. Previous studies have focused on the exploration of intracellular signaling regulatory networks, but the regulatory roles of extracellular networks have only been revealed recently. Proteoglycans, which are essential components of the extracellular matrix (ECM) and pivotal signaling molecules, are extensively involved in the process of odontogenesis. Proteoglycans are composed of core proteins and covalently attached glycosaminoglycan chains (GAGs). The core proteins exhibit spatiotemporal expression patterns during odontogenesis and are pivotal for dental tissue formation and periodontium development. Knockout of core protein genes , , , and has been shown to result in structural defects in enamel and dentin mineralization. They are also closely involved in the development and homeostasis of periodontium by regulating signaling transduction. As the functional component of proteoglycans, GAGs are negatively charged unbranched polysaccharides that consist of repeating disaccharides with various sulfation groups; they provide binding sites for cytokines and growth factors in regulating various cellular processes. In mice, GAG deficiency in dental epithelium leads to the reinitiation of tooth germ development and the formation of supernumerary incisors. Furthermore, GAGs are critical for the differentiation of dental stem cells. Inhibition of GAGs assembly hinders the differentiation of ameloblasts and odontoblasts. In summary, core proteins and GAGs are expressed distinctly and exert different functions at various stages of odontogenesis. Given their unique contributions in odontogenesis, this review summarizes the roles of proteoglycans and GAGs throughout the process of odontogenesis to provide a comprehensive understanding of tooth development.
Topics: Mice; Animals; Glycosaminoglycans; Mice, Knockout; Odontogenesis; Extracellular Matrix Proteins; Tooth Germ
PubMed: 38407002
DOI: 10.1177/00220345231224228 -
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 -
Oral Diseases Feb 2024Odontogenesis, an intricate process initiated by epithelium-mesenchyme interaction, is meticulously regulated by a cascade of regulatory mechanisms. Epigenetic... (Review)
Review
OBJECTIVES
Odontogenesis, an intricate process initiated by epithelium-mesenchyme interaction, is meticulously regulated by a cascade of regulatory mechanisms. Epigenetic modifications, especially histone modification, have been found to exhibit spatiotemporal specificity during tooth development. However, the expression patterns and roles of enzymes associated with histone modifications have yet to be systematically explored in odontogenesis. This review aims to summarize the histone-modifying enzymes in odontogenesis and their regulation mechanism during tooth development and provide the potential theoretical basis for the clinical management and intervention of dental developmental diseases.
SUBJECTS AND METHODS
This study conducted a systematic search across PubMed and Web of Science databases, utilizing the keywords "odontogenesis," "histone modification," and "enzyme" for pertinent articles.
RESULTS
No doubt histone modification contributes extensively to odontogenesis regulation, and the disturbances in histone modifications can derange the odontogenesis process.
CONCLUSION
Further studies are warranted to elucidate these roles and their potential downstream effects, positioning histone modifications as a pivotal focal point for unraveling the intricacies of tooth development and regeneration.
PubMed: 38376106
DOI: 10.1111/odi.14894 -
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 -
Medecine Sciences : M/S Jan 2024Tooth formation results from specific epithelial-mesenchymal interactions, which summarize a number of developmental processes. Tooth anomalies may thus reflect...
Tooth formation results from specific epithelial-mesenchymal interactions, which summarize a number of developmental processes. Tooth anomalies may thus reflect subclinical diseases of the kidney, bone and more broadly of the mineral metabolism, skin or nervous system. Odontogenesis starts from the 3 week of intrauterine life by the odontogenic orientation of epithelial cells by a first PITX2 signal. The second phase is the acquisition of the number, shape, and position of teeth. It depends on multiple transcription and growth factors (BMP, FGF, SHH, WNT). These ecto-mesenchymal interactions guide cell migration, proliferation, apoptosis and differentiation ending in the formation of the specific dental mineralized tissues. Thus, any alteration will have consequences on the tooth structure or shape. Resulting manifestations will have to be considered in the patient phenotype and the multidisciplinary care, but also may contribute to identify the altered genetic circuity.
Topics: Humans; Epithelium; Signal Transduction; Tooth; Odontogenesis; Cell Differentiation; Gene Expression Regulation, Developmental
PubMed: 38299898
DOI: 10.1051/medsci/2023190 -
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