During development, tooth germs undergo various morphological changes resulting from interactions between the oral epithelium and ectomesenchyme. These processes are influenced by the extracellular matrix, the composition of which, along with cell adhesion and signaling, is regulated by metalloproteinases. Notably, these include matrix metalloproteinases (MMPs), a disintegrin and metalloproteinases (ADAMs), and a disintegrin and metalloproteinases with thrombospondin motifs (ADAMTSs). Our analysis of previously published scRNAseq datasets highlight that these metalloproteinases show dynamic expression patterns during tooth development, with expression in a wide range of cell types, suggesting multiple roles in tooth morphogenesis. To investigate this, Marimastat, a broad-spectrum inhibitor of MMPs, ADAMs, and ADAMTSs, was applied to ex vivo cultures of mouse molar tooth germs. The treated samples exhibited significant changes in tooth germ size and morphology, including an overall reduction in size and an inversion of the typical bell shape. The cervical loop failed to extend, and the central area of the inner enamel epithelium protruded. Marimastat treatment also disrupted proliferation, cell polarization, and organization compared with control tooth germs. In addition, a decrease in laminin expression was observed, leading to a disruption in continuity of the basement membrane at the epithelial-mesenchymal junction. Elevated hypoxia-inducible factor 1-alpha gene (Hif-1α) expression correlated with a disruption to blood vessel development around the tooth germs. These results reveal the crucial role of metalloproteinases in tooth growth, shape, cervical loop elongation, and the regulation of blood vessel formation during prenatal tooth development.NEW & NOTEWORTHY Inhibition of metalloproteinases during tooth development had a wide-ranging impact on molar growth affecting proliferation, cell migration, and vascularization, highlighting the diverse role of these proteins in controlling development.
- MeSH
- Hypoxia-Inducible Factor 1, alpha Subunit metabolism genetics MeSH
- Matrix Metalloproteinase Inhibitors pharmacology MeSH
- Hydroxamic Acids pharmacology MeSH
- Metalloproteases metabolism genetics MeSH
- Molar embryology growth & development metabolism enzymology MeSH
- Morphogenesis MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Odontogenesis * MeSH
- Cell Proliferation * MeSH
- Gene Expression Regulation, Developmental MeSH
- Tooth Germ embryology metabolism enzymology MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
OBJECTIVES: Annotating carious lesions on images is challenging. For artificial intelligence (AI) applications, the aggregation of heterogeneous multi-examiner annotations into one single annotation (e.g. via majority voting, MV) is usually needed. We assessed different aggregation strategies for multi-examiner annotations of primary proximal carious lesions on orthoradial radiographs and Near-Infrared Light Transillumination (NILT) images. METHODS: A total of 1007 proximal surfaces from 522 extracted posterior teeth were assessed by five dentists. Histological analysis provided the gold standard. Surfaces were classified as (1) sound, (2) enamel lesion or (3) dentin lesion. Four label aggregation strategies - MV, Weighted Majority Voting (WMV), Dawid-Skene (DS), and multi-annotator competence estimation (MACE) - were applied to unimodal (radiographs, NILT) and multimodal (combined) datasets. The area under the receiver operating characteristic curve (AUROC) was the primary outcome metric. RESULTS: According to the gold standard, 637 (63 %) surfaces were sound, 280 (28 %) showed carious lesions limited to the enamel, and 90 (9 %) showed lesions extending into the dentin. For radiographs, aggregation using MACE outperformed MV, WMV and DS significantly across all lesion depths (p < 0.002). For NILT, MACE significantly outperformed MV across all lesion depths (p < 0.001) and DS for enamel and dentin lesions (p ≤ 0.002). In the multimodal dataset, DS outperformed the other label aggregation strategies across all lesion depths significantly (p < 0.05). CONCLUSIONS: The commonly applied MV may be suboptimal. There is a need for informed application of specific aggregation strategies, depending on the dataset characteristics. CLINICAL SIGNIFICANCE: Most AI applications for dental image analysis are trained on a single annotation, usually resulting from aggregated multi-examiner annotations of each image. However, since these annotations are usually aggregated in an in vivo setting where no definitive ground truth is available, the choice of aggregation strategy plays a crucial role.
- MeSH
- Dentin pathology diagnostic imaging MeSH
- Humans MeSH
- Image Processing, Computer-Assisted * methods MeSH
- Radiography, Dental MeSH
- ROC Curve MeSH
- Transillumination MeSH
- Artificial Intelligence MeSH
- Dental Caries * diagnostic imaging pathology MeSH
- Dental Enamel diagnostic imaging pathology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Úvod: V důsledku metabolických dějů dochází v živých strukturách k endogenní produkci chemiluminiscence, kterou také označujeme jako biologickou autochemiluminiscenci (BAL). Generování BAL je úzce spojeno s oxidačními procesy, tvorbou volných radikálů a obecně oxidačně-redukční homeostázou zkoumaného biologického materiálu. BAL byla již dříve studována v savčích buněčných modelech a tkáních. Doposud ovšem nebyl tento jev popsán v případě struktur zubní tkáně. Kromě endogenně generované BAL lze BAL indukovat i exogenně, a to jak fyzikálními (UV záření, mechanické poškození, teplo), tak i chemickými (oxidační činidla, např. H2O2) a biotickými (patogeny) faktory. Metodika: V předložené práci byla zkoumána endogenně produkovaná i exogenně indukovaná BAL v povrchových a vnitřních strukturách semiretinovaných a retinovaných třetích molárů, které byly indikovány k extrakci zubním lékařem pro jejich nevhodné uložení v čelisti u dvou pacientů (žena, 21 let, muž, 22 let). Detekce BAL byla provedena po mechanickém odstranění zubního plaku rotačním kartáčkem. Pomocí piezoelektrické pily byly připraveny podélné řezy vedené tak, aby došlo k odhalení všech vnitřních částí zubu. Takto připravené vzorky – celého vnitřního řezu a vnější části celého zubu – byly podrobeny detekci BAL ve světlotěsné komoře za použití fotonásobičového modulu. Následně byly vzorky ošetřeny roztokem oxidačního činidla 3% H2O2 a redukčního činidla 10 mM TCEP (tris(karboxyethyl)fosfin). Výsledky: U obou vzorků zubu bylo prokázáno, že produkují BAL. Produkce endogenní chemiluminiscence byla pozorována ve vnitřních strukturách zubu (18 600 pulzů/600 s), která byla přibližně 2,7krát vyšší než BAL detekovaná na povrchových strukturách zubu (6 900 pulzů/600 s). Po ošetření H2O2 došlo k významnému (až 14násobnému) nárůstu BAL pro vnitřní struktury zubu ve srovnání s bazální intenzitou endogenně produkované BAL. Aplikace TCEP (negativní kontrola) vedla k mírnému potlačení produkce BAL. Závěr: Výsledky této pilotní studie ukazují, že BAL může být produkována nejenom měkkými tkáněmi, ale i tvrdou zubní tkání. Získané výsledky by mohly být využity k výzkumu metabolické aktivity a reaktivity vnitřních i vnějších částí zubu, a to především v kontextu výzkumu oxidačněredukční homeostázy. Detekce BAL by také mohla být aplikována pro vývoj nových zobrazovacích technik.
Introduction: As a result of metabolic processes, the endogenous production of chemiluminescence occurs in living biological structures, which we also refer to as biological autochemiluminescence (BAL). The generation of BAL is closely connected with oxidation processes, the formation of free radicals, and in general the redox homeostasis of the investigated biological material. BAL has previously been studied in mammalian cells and tissues. So far, however, this phenomenon has not been described in dental tissue structures. In addition to endogenously generated BAL, BAL can be exogenously induced by physical (UV radiation, mechanical damage, heat), chemical (oxidizing agents, e.g. H2O2) or biotic (pathogens) factors. Methods: Endogenously and exogenously induced BAL were investigated on the surface and internal structures of semi-impacted and impacted third molars, which were indicated for extraction by a dentist due to their inappropriate placement in the jaw in two patients (a 21-year-old woman and a 22-year-old man). BAL detection was performed with samples after dental plaque was mechanically removed with a rotating brush. Using a piezosurgery unit with a saw headpiece, longitudinal sections were made to reveal all internal parts of the tooth. The samples prepared in this way – the entire internal section and the external part of the entire tooth – were subjected to BAL detection in a dark chamber using H7360-01 PMT photomultiplier. Subsequently, the samples were treated with a solution of the oxidizing agent 3% H2O2 or the reducing agent 10 mM TCEP (tris(carboxyethyl)phosphine). Results: Both tooth samples were shown to produce BAL. Endogenous chemiluminescence production was observed in the internal structures of the tooth (18,600 counts/600 s), which was 2.7-fold higher than the BAL detected on the tooth outer surfaces (6,900 counts/600 s). After H2O2 treatment, there was a significant (up to 14-fold) increase in BAL for internal tooth structures compared to the basal intensity of endogenously produced BAL. The application of TCEP (negative control) resulted in a residual suppression of BAL production. Conclusion: The results of this pilot study show that BAL can be produced not only by soft tissues but also by hard dental tissue. The obtained results could be used for further research of the metabolic activity and reactivity of the inner and outer parts of the tooth, especially in the context of redox biology research. BAL detection could also be applied in the development of new imaging techniques.
Development of dentition is a commonly studied process as a representative of the development of ectodermal derivates. A key step is the formation of a signaling center called the enamel knot (EK), which organizes tooth crown formation. In the mouse lower jaw, the anterior part of the tooth-forming region undergoes a series of complex events before the first molar primary EK can form more posteriorly and the tooth can progress through the cap stage. Although much is known about the molecular factors involved in tooth development, disentangling their specific roles is difficult. In this study, we circumvented this problem by isolating the posterior part of the tooth-forming region at embryonic day 13.5 and cultivating it in vitro. By treating them with molecules activating or inhibiting Sonic hedgehog (Shh) and fibroblast growth factor (Fgf) pathways, we demonstrate that Shh plays the role of an inhibitor of EK formation, and we suggest that the FGF pathways may have both positive and negative roles, as seen in hair. By RNA-sequencing of the cultivated isolates after 0, 16, or 24 h in vitro, respectively, we screened for genes whose expression varies with EK and cap formation and pointed to Cdkn2b and Sema3b as 2 promising candidates in this process.
- MeSH
- Fibroblast Growth Factors physiology MeSH
- Molar embryology MeSH
- Mice MeSH
- Odontogenesis * physiology genetics MeSH
- Hedgehog Proteins physiology metabolism MeSH
- Signal Transduction MeSH
- Gene Expression Regulation, Developmental MeSH
- Tooth Crown * embryology MeSH
- Dental Enamel * embryology MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Dental pulp is a valuable and accessible source of stem cells (DPSCs) with characteristics similar to mesenchymal stem cells. DPSCs can regenerate a range of tissues and their potential for clinical application in regenerative medicine is promising. DPSCs have been found to express low levels of Class II HLA-DR (MHC) molecules, making them potential candidates for allogeneic transplantation without matching the donor's tissue. Research on the correlation between non-coding RNAs (ncRNAs) and human dental pulp stem cells (DPSCs) provides promising insights into the use of these cells in clinical settings for a wide range of medical conditions. It is possible to use a number of ncRNAs in order to restore the functional role of downregulated ncRNAs that are correlated with osteoblastogenesis, or to suppress the functional role of overexpressed ncRNAs associated with osteoclast differentiation in some cases.
- MeSH
- Cell Differentiation MeSH
- Stem Cells * cytology metabolism MeSH
- Humans MeSH
- RNA, Untranslated genetics MeSH
- Regenerative Medicine * methods MeSH
- Stem Cell Transplantation methods MeSH
- Dental Pulp * cytology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Úvod a cíl: Autotransplantaci zubu můžeme v současné době pokládat za jeden z možných způsobů ošetření ztráty zubu. Tento způsob terapie se rozvíjí již více než 30 let a dostává se postupně do širšího povědomí zubních lékařů. Cílem této retrospektivní klinické studie bylo zpracovat a vyhodnotit výsledky zubní autotransplantace u dětí a dospělých pacientů s určením míry přežití autotransplantovaného zubu a míry úspěšnosti tohoto typu ošetření. Dalším cílem bylo určit specifika autotransplantací u jednotlivých věkových skupin se závěry důležitými pro klinickou praxi. Metodika: Zkoumaným souborem byli pacienti odeslaní konsekutivně k autotransplantaci zubů na specializované pracoviště v letech 2016–2021. Byla zaznamenána odbornost ošetřujícího lékaře, který pacienta k autotransplantaci indikoval, vhodnost a proveditelnost transplantace a donorová a příjmová oblast zubního transplantátu. Počátkem roku 2022 probíhalo klinické a rentgenologické hodnocení autotransplantovaných zubů. Pacienti byli rozděleni na dvě skupiny podle věku v době autotransplantace, a to do 18 let a více než 18 let. Výsledky: Celkově bylo k autotransplantaci delegováno 73 pacientů ve věkovém rozmezí 10–59 let. Věkový průměr byl 21,4 let s mediánem 17 let. U 12 pacientů nebyla autotransplantace doporučena. Celkově bylo provedeno 68 autotransplantací zubů, 12 jich však nesplňovalo minimální období sledování (šest měsíců po autotransplantaci). Celkově bylo tedy zhodnoceno 56 dentálních autotransplantátů. Ve skupině dětí se jednalo o 27 jedinců ve věku 10–17 let, u kterých byla provedena autotransplantace alespoň jednoho stálého zubu. Celkem bylo transplantováno 34 zubů. Vyhodnocení transplantovaných zubů proběhlo po 6 až 50 měsících od transplantace s průměrem 24 měsíců. Míra přežití dosahovala 100 %, míra úspěšnosti 91 %. Ve skupině dospělých se jednalo o 22 jedinců ve věku 18–59 let a celkem bylo transplantováno 22 zubů. Vyhodnocení transplantovaných zubů proběhlo po 6 až 72 měsících od transplantace s průměrem 33 měsíců. Míra přežití dosahovala 95 %, míra úspěšnosti 77 %. Závěr: Využití autotransplantátu k náhradě nezaloženého nebo ztraceného zubu nejčastěji indikovali ortodontisté. U pacientů ve věku do 18 let převažují jako donorová i příjmová oblast premoláry. U pacientů nad 18 let věku převažují jako donorová oblast třetí moláry a jako příjmová oblast moláry v dolní čelisti. U obou věkových skupin je vysoká míra přežití i úspěšnosti autotransplantátu, a proto lze tento postup považovat za spolehlivou metodu náhrady zubu.
Introduction, aim: At present, tooth autotransplantation is considered one of the therapeutic methods for the replacement of lost teeth. In the last 30 years, the method of tooth autotransplantation has been developed and refined and has become a basic knowledge of dental practitioners. The aim of this clinical retrospective study was to examine children and adult patients with tooth autotransplantation and obtain survival and success rates. Another aim was to determine other specifics of autotransplantation in each group with conclusions relevant for clinical practice. Methods: The study population consisted of the patients referred consecutively for tooth autotransplantation to a specialist department between years 2016 and 2021. The specialization of the reffering dentist, the suitability and feasibility of the transplantation, and the donor and recipient area of the tooth graft were recorded. In 2022, clinical and radiological evaluation of the autotransplanted teeth was performed. Patients were divided into two groups according to age in time of autotransplantation, namely under 18 years and over 18 years. Results: Overall, 73 patients in the age range of 10–59 years were referred for autotransplantation. The mean age was 21.43 years with a median age of 17 years. Autotransplantation was not recommended in 12 patients. A total of 68 autotransplantations were performed, but at the time of examination, 12 did not meet the minimum 6-month follow up, so they were excluded from the evaluation. A total of 56 autotransplants were evaluated. In the group of children, there were 27 patients aged 10–17 years who underwent autotransplantation of at least one permanent tooth. A total of 34 teeth were transplanted. The evaluation of the transplanted teeth was performed 6–50 months after the transplantation with a mean follow-up time of 24 months. The survival rate was 100% and the success rate was 91%. The adult group consisted of 22 patients aged 18–59 years and a total of 22 teeth were transplanted. The evaluation of the transplanted teeth was performed 6–72 months after transplantation with a mean of 33 months. The survival rate was 95%, the success rate 77%. Conclusion: The use of autograft to replace undeveloped or lost teeth was most often indicated by orthodontists. In the patients under 18 years of age, the premolars are the predominant donor area and recipient area. In patients over 18 years of age, the third molars are the predominant donor area and the mandibular molars the predominant recipient area. Both age groups have high survival and success rates of autograft and this procedure can be considered as a predictable method of tooth replacement.
- MeSH
- Survival Analysis MeSH
- Autografts diagnostic imaging statistics & numerical data MeSH
- Transplantation, Autologous * methods statistics & numerical data MeSH
- Adult MeSH
- Kaplan-Meier Estimate MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Postoperative Period MeSH
- Retrospective Studies MeSH
- Tooth Root growth & development transplantation MeSH
- Tooth * diagnostic imaging transplantation MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Clinical Study MeSH
- MeSH
- Neovascularization, Physiologic MeSH
- Intravital Microscopy methods MeSH
- Clinical Clerkship MeSH
- Humans MeSH
- Disease Models, Animal MeSH
- Mice MeSH
- Regenerative Endodontics * methods education MeSH
- Tissue Scaffolds MeSH
- Stem Cell Transplantation methods MeSH
- Tooth Root surgery MeSH
- Tooth Germ MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- MeSH
- Apicoectomy * classification methods MeSH
- Tooth Apex surgery MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- MeSH
- Chronic Periodontitis * surgery diagnosis MeSH
- Middle Aged MeSH
- Humans MeSH
- Periodontal Dressings MeSH
- Equipment Failure MeSH
- Oral Surgical Procedures methods MeSH
- Tooth Root * surgery pathology MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
