Enamel Matrix Derivative Research Articles

Effects of Advanced Platelet Rich Fibrin (A-PRF+), Enamel Matrix Derivative (EMD) and Open Flap Debridement on clinical and wound healing parameters in molar furcation sites: A case series from a RCT study

AimTo study effects of advanced platelet rich Fibrin (A-PRF+) and enamel matrix derivative (EMD) compared to open flap debridement (OFD) alone in molar furcation sites grade II on clinical and wound healing parameters.Materials and methodsA randomized controlled trial was designed. Eligible patients were randomly allocated in one of three treatment groups: A-PRF+, EMD or OFD. The patients and clinical examiners were blinded for the treatment received. A minimally invasive microsurgical approach was performed for the three modalities. Clinical measurements were scored at baseline and 6 months postoperatively. The clinical healing of each furcation was scored via Early Wound Healing Index on day 3, 1 week, 2 weeks and 6 weeks.Results17 patients (A-PRF+ n = 6, EMD n = 5, OFD n = 6) completed the 6 months follow-up. The further completion of the trial had to be cancelled due to the COVID-19 pandemic. In three patients in the A-PRF+ group, the grade II of the treated furcation regressed to grade I; the corresponding number in the EMD and OFD groups were zero and one respectively. Further, 3, 1 and 4 patients in the PRF, EMD and OFD groups respectively, showed a gain of bone level ≥1 mm. The defects in the A-PRF+ group showed delayed early healing compared to EMD and OFD groups.ConclusionThe case series (RCT design) suggest a slight advantage for A-PRF+ over EMD and OFD, regarding the regressing of a furcation II to grade I, however this treatment showed delayed early wound healing compared to EMD or OFD.Clinical Trial Registrationhttps://www.isrctn.com/, identifier ISRCTN13520922.

EMD-liquid contributes to tissue thickness gain in soft tissue augmentation using a collagen matrix.

To investigate the function of enamel matrix derivative (EMD)-liquid compared to EMD-gel (original Emdogain® with polyglycolic acid-carrier) in inducing soft tissue regeneration using a rat dorsal model. Four subcutaneous pouches were created through dorsal skin incisions in 18 female Wistar rats and randomly allocated to the following groups: (1) sterile saline + non-crosslinked collagen matrix (CM), (2) EMD-gel + CM, and (3) EMD-liquid + CM. After 2 and 4weeks of healing, the specimens were harvested and stained with Goldner's trichrome, hematoxylin and eosin, and were immunohistochemically stained with an anti-CD31 antibody. The EMD-liquid group showed the thickest connective tissue compared to the other groups, with statistical significance both at 2 (p < 0.001) and 4weeks (p = 0.011 and 0.023, respectively). The number of multinucleated giant cells was not significantly different among the groups for both periods. Moreover, there was a tendency to have more blood vessels over a longer period, and the highest number of blood vessels was observed in the EMD-liquid group at 4weeks (p = 0.009 and 0036, respectively). EMD-liquid-treated CM is advantageous compared to using CM alone or EMD-gel-treated CM, owing to the histomorphometric results that show significantly increased soft tissue thickness and number of blood vessels when EMD-liquid was pre-primed to CM. EMD with a liquid carrier may be an appropriate biologic supplement to provide cell-inducing properties to the CM scaffold and is clinically more beneficial for phenotype modification therapy than CM only and EMD-gel-treated CM.

The role of FGF9-mediated TGF-β1/Smad signaling in enamel hypoplasia induced by exposure to fluoride and SO2 in rats

Many geographical areas of the world are polluted by both fluoride and sulfur dioxide (SO2). However, the effects of simultaneous exposure to fluoride and SO2 on teeth are unknown. Fibroblast growth factor-9 (FGF9) and transforming growth factor-β1 (TGF-β1) are key signaling molecules in enamel development. The purpose of the study was to explore the effects of co-exposure to fluoride and sulfur dioxide on enamel and to investigate the role and mechanism of FGF9 and TGF-β1. First, sodium fluoride (NaF) and SO2 derivatives were used to construct rat models and evaluate the enamel development of rats. Then, TGF-β1 (cytokine) treatment, SIS3 (inhibitor) treatment and FGF9 gene knockdown were used to explore the mechanism of enamel damage in vitro. The results showed that enamel column crystals in the exposed group were characterized by enamel hypoplasia, as indicated by alterations such as disarrangement of enamel column crystals, space widening and breakage. Ameloblasts also showed pathological changes such as ribosome loss, mitochondrial swelling, nuclear fragmentation and chromatin aggregation. The protein expression of FGF9 was higher and the protein expression of AMBN, TGF-β1 and p-Smad2/3 protein was lower in the groups treated with fluoride and SO2 individually or in combination compared with the control group. Further studies showed that TGF-β1 significantly upregulated p-Smad2/3 and AMBN protein expression and reduced the inhibitory effects of fluoride and SO2; furthermore, SISI blocked the effect of TGF-β1. In addition, knockdown of FGF9 upregulated TGF-β1 protein expression, further activated Smad2/3 phosphorylation, eliminated the inhibitory effects of fluoride and SO2, and increased the protein expression of AMBN. In brief, the study confirms that co-exposure to fluoride and SO2 can result in enamel hypoplasia in rats and indicates that the underlying mechanism may be closely related to the effect of FGF9 on enamel matrix protein secretion through inhibition of the TGF-β1/Smad signaling pathway.

Tmem2 Deficiency Leads to Enamel Hypoplasia and Soft Enamel in Mouse

Teeth consist of 3 mineralized tissues: enamel, dentin, and cementum. Tooth malformation, the most common craniofacial anomaly, arises from complex genetic and environmental factors affecting enamel structure, size, shape, and tooth eruption. Hyaluronic acid (HA), a primary extracellular matrix component, contributes to structural and physiological functions in periodontal tissue. Transmembrane protein 2 (TMEM2), a novel cell surface hyaluronidase, has been shown to play a critical role during embryogenesis. In this study, we demonstrate Tmem2 messenger RNA expression in inner enamel epithelium and presecretory, secretory, and mature ameloblasts. Tmem2 knock-in reporter mice reveal TMEM2 protein localization at the apical and basal ends of secretory ameloblasts. Micro–computed tomography analysis of epithelial-specific Tmem2 conditional knockout (Tmem2-CKO) mice shows a significant reduction in enamel layer thickness and severe enamel deficiency. Enamel matrix protein expression was remarkably downregulated in Tmem2-CKO mice. Scanning electron microscopy of enamel from Tmem2-CKO mice revealed an irregular enamel prism structure, while the microhardness and density of enamel were significantly reduced, indicating impaired ameloblast differentiation and enamel matrix mineralization. Histological evaluation indicated weak adhesion between cells and the basement membrane in Tmem2-CKO mice. The reduced and irregular expressions of vinculin and integrin β1 suggest that Tmem2 deficiency attenuated focal adhesion formation. In addition, abnormal HA accumulation in the ameloblast layer and weak claudin 1 immunoreactivity in Tmem2-CKO mice indicate impaired tight junction gate function. Irregular actin filament assembly was also observed at the apical and basal ends of secretory ameloblasts. Last, we demonstrated that Tmem2-deficient mHAT9d mouse ameloblasts exhibit defective adhesion to HA-containing substrates in vitro. Collectively, our data highlight the importance of TMEM2 in adhesion to HA-rich extracellular matrix, cell-to-cell adhesion, ameloblast differentiation, and enamel matrix mineralization.

Re-understanding the role of enamel matrix proteins in periodontal regeneration

Enamel matrix proteins (EMP) are deposited on the surface of developing roots before dentin formation and may play a role in osteogenesis. Amelogenins (Am) are the main and active component in EMPs. Studies had showed great clinical values of EMPs in periodontal regenerative treatment and other fields. By affecting the expression of growth factors and inflammatory factors, EMPs could act on various periodontal regeneration-related cells to promote angiogenesis, anti-inflammation, bacteriostasis and tissue healing, achieving the clinical effect of periodontal tissue regeneration (newly generated cements and alveolar bones as well as functionally penetrated periodontal ligament). EMPs alone or combined with bone graft material and barrier can be used for regenerative surgical treatment in intrabony defects and degree Ⅱ furcation-involved at maxillary buccal or mandibular teeth. EMPs can also be adjunctively used to treat recession type 1 or 2 gingival recessions, forming periodontal regeneration on the exposed root surface. Through a comprehensive understanding of the principle and current clinical application of EMPs on periodontal regeneration, we can look forward to their future development. The development of recombinant human amelogenin to replace animal-derived EMPs through bioengineering technologies, the study of the clinical application of EMPs combined with other collagen biomaterials, and the specific application of EMPs in severe soft and hard periodontal tissue defects and peri-implant lesions are all important development directions of future EMPs-related researches.

Enamel matrix derivative for alveolar ridge preservation: A randomized controlled trial.

The aims of this clinical trial were to evaluate the radiographic dimensional changes in alveolar ridge and patient-reported outcomes following tooth extraction and alveolar ridge preservation (ARP) using either deproteinized bovine bone mineral (DBBM) with EMD or DBBM alone. Participants requiring at least one posterior tooth extraction and ARP were randomly allocated into two treatment groups: ARP using either DBBM with EMD or DBBM alone. Cone-beam computed tomography (CBCT) images were recorded immediately prior to extraction and at 6 months. Changes in alveolar ridge height (ARH) and alveolar ridge width (ARW) at 1, 3, and 5 mm were recorded. A total of 18 participants with 25 preserved sites were evaluated. ARH and ARW changed significantly from baseline to 6 months for both treatment groups but the difference between the groups was not statistically significant over the 6-month follow-up period (ARH: DBBM/EMD 1.26 ± 1.53 mm vs. DBBM 2.26 ± 1.60 mm; ARW-1 DBBM/EMD 1.98 ± 1.80 mm vs. DBBM 2.34 ± 1.89 mm). A significant difference, favoring DBBM with EMD group, was observed in percentage of sites that had less than 1 mm loss in ARH (54.5% sites in DBBM/EMD group vs. 14.3% sites in DBBM alone group). The participants' perception of bruising, bleeding, and pain in the first two postoperative days was significantly in favor of DBBM alone group. There were no significant differences in radiographic mean measurements of ARH and ARW following ARB with DBBM and EMD or DBBM alone.

Influence of Occlusal Hypofunction on Alveolar Bone Healing in Rats.

The aim of this in vivo study was to investigate the effect of occlusal hypofunction on alveolar bone healing in the absence or presence of an enamel matrix derivative (EMD). A standardized fenestration defect over the root of the mandibular first molar in 15 Wistar rats was created. Occlusal hypofunction was induced by extraction of the antagonist. Regenerative therapy was performed by applying EMD to the fenestration defect. The following three groups were established: (a) normal occlusion without EMD treatment, (b) occlusal hypofunction without EMD treatment, and (c) occlusal hypofunction with EMD treatment. After four weeks, all animals were sacrificed, and histological (hematoxylin and eosin, tartrate-resistant acid phosphatase) as well as immunohistochemical analyses (periostin, osteopontin, osteocalcin) were performed. The occlusal hypofunction group showed delayed bone regeneration compared to the group with normal occlusion. The application of EMD could partially, but not completely, compensate for the inhibitory effects of occlusal hypofunction on bone healing, as evidenced by hematoxylin and eosin and immunohistochemistry for the aforementioned molecules. Our results suggest that normal occlusal loading, but not occlusal hypofunction, is beneficial to alveolar bone healing. Adequate occlusal loading appears to be as advantageous for alveolar bone healing as the regenerative potential of EMD.

The Combined Effects of Hydraulic Calcium Silicate Cement and Enamel Matrix Derivative Regarding Osteogenic and Dentinogenic Differentiation on Human Dental Pulp Stem Cells.

The ideal treatment option for immature necrotic permanent teeth is regeneration of the pulp-dentin complex. Mineral trioxide aggregate (MTA), the conventional cement used for regenerative endodontic procedures, induces hard tissue repair. Various hydraulic calcium silicate cements (HCSCs) and enamel matrix derivative (EMD) also promote osteoblast proliferation. The purpose of the present study was to determine the osteogenic and dentinogenic potential of commercially distributed MTA and HCSCs when applied in combination with Emdogain gel on human dental pulp stem cells (hDPSCs). The presence of Emdogain resulted in greater cell viability, and higher alkaline phosphatase activity was detected in the Emdogain-supplemented groups in the early days of cell culture. On qRT-PCR, the groups treated, respectively, with Biodentine and Endocem MTA Premixed in the presence of Emdogain showed an increased expression of the dentin formation marker DSPP, and the group treated with Endocem MTA Premixed in the presence of Emdogain showed an upregulated expression of the bone formation markers OSX and RUNX2. In an Alizarin Red-S staining assay, all of the experimental groups exhibited a greater formation of calcium nodules when treated in combination with Emdogain. Overall, the cytotoxicity and osteogenic/odontogenic potential of HCSCs were similar to that of ProRoot MTA. The addition of the EMD increased the osteogenic and dentinogenic differentiation markers.

Retracted: Enamel Matrix Derivatives for Periodontal Regeneration: Recent Developments and Future Perspectives.

[This retracts the article DOI: 10.1155/2022/8661690.].

Enam expression is regulated by Msx2.

The precise formation of mineralized dental tissues such as enamel and/or dentin require tight transcriptional control of the secretion of matrix proteins. Here, we have investigated the transcriptional regulation of the second most prominent enamel matrix protein, enamelin, and its regulation through the major odontogenic transcription factor, MSX2. Using in vitro and in vivo approaches, we identified that (a) Enam expression is reduced in the Msx2 mouse mutant pre-secretory and secretory ameloblasts, (b) Enam is an early response gene whose expression is under the control of Msx2, (c) Msx2 binds to Enam promoter in vitro, suggesting that enam is a direct target for Msx2 and that (d) Msx2 alone represses Enam gene expression. Collectively, these results illustrate that Enam gene expression is controlled by Msx2 in a spatio-temporal manner. They also suggest that Msx2 may interact with other transcription factors to control spatial and temporal expression of Enam and hence amelogenesis and enamel biomineralization.

Enhancing attachment of human gingival fibroblasts to periodontally compromised teeth: A comparative analysis of hyaluronic acid, EDTA, enamel matrix derivatives

BackgroundGingival recession is a characteristic indicator of periodontitis and one of the factors that contributes to increased tooth clinical crown length. Patients with root exposure frequently undergo periodontal surgical procedures in addition to adjunctive therapy to increase root coverage area and soft tissue stability. PurposeThis study aimed to evaluate fibroblast-root surface adhesion and determine whether periodontitis-damaged root surface microstructure can be restored using ethylenediaminetetraacetic acid (EDTA) and an enamel matrix derivative (EMD), individually or in combination. Material and methodsTeeth extracted from patients with periodontal disease were used to create 60 samples, with each group containing six specimens. The test groups were provided root planing or root condition-specific materials (hyaluronic acid [HA], 24% EDTA, EMD, or EDTA/EMD) for varying treatment time periods. In contrast, the control group did not undergo any surface modifications. The samples and fibroblast cells were incubated for 72 h. The number of living cells on the root surface in each group was calculated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (cell viability assessment). ResultsThe control, root planing, and EMD groups showed that the root surfaces treated with EDTA for 4 min had significantly better cell adhesion. Surface EDTA treatment for 2 min significantly promoted cell attachment compared to root planing treatment. The root surfaces modified with EDTA/EMD for 2 and 4 min showed significantly improved cellular migration and adhesion compared to the root surface treated with root planing. ConclusionEDTA and EDTA/EMD substantially affected the root surface, which was related to the length of the treatment process. This effect shifts the surface properties, alters fibroblast interactions with the root surface, and recruits more cells to cover a larger area.

Evidentiary manoeuvrings of neoteric polymer: Emdogain – An Annotation

Enamel Matrix Derivatives (EMD) is a novel biomaterial that has been discovered in the late ’90 s and has found numerous uses in the field of periodontics. It is mainly used in areas that require natural regeneration and healing. It has found applications in other branches of dentistry, such as; wound healing, regenerative procedures, endodontics, pedodontics, and others. It mainly consists of amelogenins and other proteins such as amelin, enamelin, tufetelin etc. It is known to increase cementogenesis and improve periodontal attachment. The amount of research done on this product is very little and very scattered. The maximum amount of research has been done regarding its use in periodontic surgery and other related procedures since it had been initially discovered as a material that would increase periodontal attachment. Given its various biological properties, it is safe to say that it has the potential to succeed in other branches. Our review, therefore, aims to collect and present the research performed and ongoing research potential regarding EMD products, which are now available in a gel-based form known as Emdogain.

Association between defect morphology and healing of intrabony defects treated with minimally invasive non-surgical therapy: A pilot exploratory analysis of two cohorts.

The aim of this study was to explore the associations between defect morphology (defined by clinical and radiographic parameters) and the healing of periodontal intrabony defects treated with minimally invasive non-surgical therapy (MINST). MINST has shown to result in favorable clinical and radiographic improvements in intrabony defects. However, it is not clear which types of intrabony defects are most suitable for this treatment. Clinical and radiographic analyses were carried out in a total of 71 intrabony defects treated with MINST belonging to two previously published studies. Baseline defect characteristics were analyzed and related to clinical and radiographic outcomes at 12 months post-MINST with or without adjunctive enamel matrix derivative. No associations were detected between defect depth, angle and predicted number of walls and clinical and radiographic healing 12 months post-MINST. No evidence emerged for associations between defect characteristics and healing following MINST. These data seem to suggest that factors other than defect morphology may influence treatment response to MINST.

The influence of interradicular anatomy on the predictability of periodontal regenerative therapy of furcation defects: a retrospective, multicenter clinical study

BackgroundThe relationship between the anatomy of the interradicular space and success in regenerative therapy of furcation defects is discussed in this paper. The goal of this retrospective, multicenter clinical study is to clinically evaluate the relationship between the interradicular conformation and regenerative therapy success with the use of a novel measurement method.MethodsOne hundred thirty-eight radiographs of mandibular molars with furcation defects that had been treated with regenerative therapy were collected from six clinical centers. Data on the type of therapy and clinical parameters before and after treatment (follow-up of at least 12 months) were collected. The radiographs (before surgery and at least 12 months postoperatively) were measured with a visual evaluation method by a blind operator using graphics software.ResultsSuccess, defined as a reduction in horizontal and vertical furcation involvement, decrease in probing depths, and increase in clinical attachment level, was statistically assessed on 138 regenerated molars sites and were related to clinical variables such as age, sex, center, and treatment. No correlation was found between success in regenerative therapy and the conformation of the interradicular space, measured with a visual ratio method and a standard linear measurement.At the univariate analysis, the parameters that had a correlation with success were center, extent of furcation involvement, treatment, and sex. The use of enamel matrix derivative (EMD) seemed to be the most favorable therapy, with increase in CAL gain and reduction of vertical or horizontal furcation involvement.ConclusionsThe regenerative outcome was not significantly influenced by the anatomy of furcation. The center, the degree of furcation involvement, sex, and treatment (EMD) were significantly associated with higher success of periodontal regeneration.

Long-term stability of infrabony defects treated with enamel matrix derivative alone: A retrospective two-centre cohort study.

To assess the long-term stability of attachment gain in infrabony defects (IBDs) 10 years after regenerative treatment with an enamel matrix derivative (EMD) alone. Two centres (Frankfurt [F] and Heidelberg [HD]) invited patients for re-examination 120 ± 12 months after regenerative therapy. Re-examination included clinical examination (periodontal probing depths (PPD), vertical clinical attachment level (CAL), plaque index (PlI), gingival index (GI), plaque control record, gingival bleeding index and periodontal risk assessment) and review of patient charts (number of supportive periodontal care [SPC] visits). Both centres included 52 patients (29 female; median baseline age: 52.0 years; lower/upper quartile: 45.0/58.8 years; eight smokers), each contributing one IBD. Nine teeth were lost. For the remaining 43 teeth, regenerative therapy showed significant CAL gain after 1 year (3.0; 2.0/4.4 mm; p < .001) and 10 years (3.0; 1.5/4.1 mm; p < .001) during which CAL remained stable (-0.5; -1.0/1.0 mm; p = 1.000) after an average SPC of 9 years. Mixed-model regression analyses revealed a positive association of CAL gain from 1 to 10 years with CAL 12 months post operation (logistic: p = .01) as well as a higher probability for CAL loss with an increasing vertical extent of a three-walled defect component (linear: p = .008). Cox proportional hazard analysis showed a positive association between PlI after 12 months and tooth loss (p = .046). Regenerative therapy of IBDs showed stable results over 9 years. CAL gain is associated with CAL after 12 months and decreasing initial defect depth in a three-walled defect morphology. Tooth loss is associated with PlI 12 months post operation. DRKS00021148 (URL: https://drks.de).

Enamel Matrix Derivatives as an Adjunct to Alveolar Ridge Preservation—A Systematic Review

To systematically assess the current evidence regarding the adjunctive application of enamel matrix derivatives (EMDs) during alveolar ridge preservation (ARP) following tooth extraction. A comprehensive literature search was conducted in MEDLINE, Cochrane Library, PsycINFO, Web of Science, Google Scholar, and Scopus to identify relevant randomized controlled clinical trials (RCTs). The primary outcome parameters of this systematic review were histomorphometric and radiographic data; secondary outcomes were the feasibility of implant placement after ARP as well as patient-related outcomes such as postoperative discomfort. The search identified 436 eligible articles published from 2011 to 2022, but only five were ultimately included for data extraction (146 patients). Given the substantial heterogeneity among the included studies, no meta-analysis could be performed. The authors' qualitative analysis showed marginally improved outcomes regarding an increased percentage of new bone formation after tooth extraction and a reduction in postoperative discomfort. Given the potential value of EMDs in other fields of regenerative dentistry, more consideration should be given to EMDs as an adjunctive treatment option in ARP. However, more well-controlled randomized clinical trials are necessary to evaluate the exact potential and impacts of EMDs.

Human Trials on the Prevention of Tunnel Widening by the Emdogain in Anterior Cruciate Ligament Reconstruction.

Background Although anterior cruciate ligament reconstruction (ACLR) is an established procedure, some problems remain, such as bone tunnel widening after ACLR. In animal studies, Emdogain (EMD) prevented tunnel widening by promoting tendon-bone healing. This study aimed to evaluate the effects of EMD on the prevention of tunnel widening after anterior cruciate ligament (ACL) injury in humans. Methods Nineteen patients who underwent ACLR were included. Seven patients in the EMD group were administered EMDs into the femoral tunnel during ACLR, while 12 patients in the control group were not administered EMDs. After surgery, at two and four weeks and three, six, and 12 months, femoral and tibial tunnel widening were evaluated on computed tomography images. Anteroposterior laxity and clinical scores such as the Lysholm score, the International Knee Documentation Committee (IKDC) subjective form, and the Knee Injury and Osteoarthritis Outcome Score (KOOS) were assessed beforesurgery and 12 months postoperatively. Results Tunnel widening on the femoral side was significantly smaller in the EMD group than in the control group at two weeks. However, there was no significant difference between the two groups at 12 months. There were no significant differences in anteroposterior laxity and clinical scores between the groups before and 12 months after surgery. Conclusion EMD administration into the bone tunnel did not prevent tunnel widening at 12 months after ACLR, although tunnel widening of the femoral tunnel was reduced by EMD administration in the early phase.

The Effects of Alloplastic Bone Substitute and Enamel Matrix Derivative on the Preservation of Single Anterior Extraction Sockets: A Tomographic Evaluation.

This study was designed to assess the use of enamel matrix derivative (EMD; Emdogain, Straumann) and alloplastic bone substitute (BoneCeramic [BC], Straumann) in postextraction alveolar sockets. A total of 45 patients requiring anterior single tooth extractions and subsequent implant placement were recruited and randomly assigned to one of three treatment groups. Postextraction sockets were filled with BC or BC + EMD, or were left to heal spontaneously. Tomographic dimensional changes were measured immediately following tooth extraction and at the 6-month follow-up. Computed tomographic (CT) scans were taken with a radiographic stent within 48 hours of extraction (CT1) and at 6 months (CT2). Paired comparisons related to the mean horizontal reduction of the vestibular crest (VC) showed significant differences between sockets left to heal spontaneously (Group 1) and the two groups filled with BC (Group 2) and BC + EMD (Group 3): 1.7 mm for Group 1 and 0.9 mm for Groups 2 and 3 (P < .05). Thus, the use of alloplastic bone substitute alone or with EMD resulted in better preservation of postextraction socket dimensions. No differences in socket preservation were found between Group 2 (BC) and Group 3 (BC + EMD). Int J Periodontics Restorative Dent 2023;43:e117-e124. doi: 10.11607/prd.5820.

Deciphering the functions of Stromal Interaction Molecule-1 in amelogenesis using AmelX-iCre mice.

Introduction: The intracellular Ca2+ sensor stromal interaction molecule 1 (STIM1) is thought to play a critical role in enamel development, as its mutations cause Amelogenesis Imperfecta (AI). We recently established an ameloblast-specific (AmelX-iCre) Stim1 conditional deletion mouse model to investigate the role of STIM1 in controlling ameloblast function and differentiation in vivo (Stim1 cKO). Our pilot data (Said et al., J. Dent. Res., 2019, 98, 1002-1010) support our hypothesis for a broad role of Stim1 in amelogenesis. This paper aims to provide an in-depth characterization of the enamel phenotype observed in our Stim1 cKO model. Methods: We crossed AmelX-iCre mice with Stim1-floxed animals to develop ameloblast-specific Stim1 cKO mice. Scanning electron microscopy, energy dispersive spectroscopy, and micro- CT were used to study the enamel phenotype. RNAseq and RT-qPCR were utilized to evaluate changes in the gene expression of several key ameloblast genes. Immunohistochemistry was used to detect the amelogenin, matrix metalloprotease 20 and kallikrein 4 proteins in ameloblasts. Results: Stim1 cKO animals exhibited a hypomineralized AI phenotype, with reduced enamel volume, diminished mineral density, and lower calcium content. The mutant enamel phenotype was more severe in older Stim1 cKO mice compared to younger ones and changes in enamel volume and mineral content were more pronounced in incisors compared to molars. Exploratory RNAseq analysis of incisors' ameloblasts suggested that ablation of Stim1 altered the expression levels of several genes encoding enamel matrix proteins which were confirmed by subsequent RT-qPCR. On the other hand, RT-qPCR analysis of molars' ameloblasts showed non-significant differences in the expression levels of enamel matrix genes between control and Stim1-deficient cells. Moreover, gene expression analysis of incisors' and molars' ameloblasts showed that Stim1 ablation caused changes in the expression levels of several genes associated with calcium transport and mitochondrial kinetics. Conclusions: Collectively, these findings suggest that the loss of Stim1 in ameloblasts may impact enamel mineralization and ameloblast gene expression.

Research progress in the pathogenesis mechanism of dental fluorosis

Dental fluorosis is a developmental disturbance of dental enamel caused by excessive fluoride intake during tooth development, leading to the changes in morphology, structure and function of tooth enamel, which can affect the aesthetics and function of teeth. There are many factors which may account for the occurrence of dental fluorosis. However, the pathogenesis mechanism underlying dental fluorosis has not been fully clarified.In recent years, researches in the fields of fluoride-induced stress response pathways, signaling pathways and apoptosis at the molecular and genetic level had provided extensive knowledge of dental fluorosis. This article focuses on the latest research progress in the mechanism of dental fluorosis, which include the effects of fluoride on ameloblasts and enamel matrix proteins, genetic polymorphism and dietary nutrients, in order to provide new references for the targeted prevention and treatment of dental fluorosis.