RARE DISEASE
Dentinogenesis imperfecta type 2
Dentinogenesis imperfecta type 2
Dentinogenesis imperfecta type 2
Synonyms: Capdepont teeth, DGI-2, DI-2, Dentinogenesis imperfecta, Shields type 2
Synonyms: Capdepont teeth, DGI-2, DI-2, Dentinogenesis imperfecta, Shields type 2
Synonyms: Capdepont teeth, DGI-2, DI-2, Dentinogenesis imperfecta, Shields type 2
Drug discovery
47
papers
On emerging therapies
Overview
Dentinogenesis Imperfecta Type 2 (DGI-2) is a severe autosomal dominant genetic disorder caused by DSPP gene mutations, disrupting dentin formation. It presents with amber or blue-gray translucent teeth, bulbous crowns, cervical constriction, and pulp obliteration radiographically. Unlike DGI-1, it lacks systemic features of osteogenesis imperfecta. Early enamel loss leads to rapid attrition, abscesses, and structural compromise. Diagnosis combines clinical, radiographic, and genetic testing. Management focuses on preserving tooth structure and function through restorative care [1][2][9][13].
Therapies
Early intervention with stainless steel crowns (primary molars) and composite restorations (anterior teeth) [3][11][17].
Later-stage prosthodontic rehabilitation (veneers, implants) and multidisciplinary care [4][8][12].
Preventive measures: fluoride therapy, dietary counseling, and 6-month dental reviews [5][12][16].
Categories: rare genetic diseases, rare odontological diseases
Research Papers
47 drug discovery papers about Dentinogenesis imperfecta type 2. Recent publications:
47 drug discovery papers about Dentinogenesis imperfecta type 2. Recent publications:
categories:
Small molecules
small molecules
2026-03-07 | Calcium phosphate polymer induced liquid precursor improves dentin bonding performance of primary teeth with dentinogenesis imperfecta type II.
OBJECTIVES: The current study aims to assess the dentin bonding performance of primary molars with dentinogenesis imperfecta type II (DGI-II). Moreover, we assess the efficacy of calcium phosphate polymer induced liquid precursor (Ca/P-PILP), a biomimetic remineralization material, in improving the resin bonding performance of DGI-II dentin. MATERIALS AND METHODS: Dentin specimens from normal and DGI-II primary molars were treated with either Ca/P-PILP or double-distilled water. Morphology of these dentin specimens were observed using scanning electron microscopy (SEM), and the calcium and phosphorus contents were determined by energy-dispersive X-ray spectroscopy (EDS). Micro-tensile bond strength (µTBS) analysis was conducted to evaluate the resin bonding strength of dentin. RESULTS: SEM results showed that compared with normal dentin, DGI-II dentin exhibited significantly fewer dentinal tubules with nearly no intact tubular structures. Meanwhile, the dentin collagen fibers exhibited disorganized arrangement and compromised structural integrity. Compared with normal dentin, DGI-II dentin displayed inferior bonding performance with resin as shown by µTBS analysis, and EDS analyses showed that DGI-II dentin contained lower calcium and phosphorus contents. After treatment with Ca/P-PILP, the calcium and phosphorus contents of DGI-II dentin were significantly increased as shown by EDS analyses, and µTBS analysis showed that the bonding performance of DGI-II dentin was improved, while no notable effect was observed in normal dentin. CONCLUSIONS: Primary molars with DGI-II display structural defects and reduced calcium and phosphorus contents in dentin. The reduced mineral contents are partially responsible for the compromised bonding performance of DGI-II dentin, for Ca/P-PILP which effectively enhances the mineral contents of DGI-II dentin improves the resin bonding performance of DGI-II dentin.
2025-12-24 | Inositol-requiring enzyme 1 alpha is essential for dentinogenesis.
Inositol-requiring enzyme 1 alpha (IRE1α), encoded by endoplasmic reticulum (ER) to nucleus signaling 1 (Ern1) gene, is the most conserved sensor of ER stress. IRE1α-initiated signaling pathways contribute to functional maturation of secretory cells and have been implicated in various human diseases. In this study, we examined the roles of IRE1α in odontoblast development and dentin formation in wild-type mice as well as in Dspp P19L mutant mice, which express a pathogenic variant of dentin sialophosphoprotein (P19L-DSPP) and exhibit a dentinogenesis imperfecta (DGI)-like phenotype. Western-blotting and stains-all staining analyses were used to assess whether secretion of mutant P19L-DSPP was impaired in dental pulp cells containing odontoblasts from Dspp P19L/P19L mice compared with Dspp +/+ controls. Immunohistochemistry and reverse-transcription PCR were performed to examine changes in IRE1α and its downstream target X-box binding protein 1 (XBP1) in P19L-DSPP mutant mice. To further investigate the roles of IRE1α in tooth development, we generated 2.3 Col1-Cre;Ern1 fl/fl and compound 2.3 Col1-Cre;Ern1 fl/fl ;Dspp P19L/+ mice. Structural and histological changes in mandibular molars were analyzed using plain X-ray radiography, micro-computed tomography (µCT), and histology. Additionally, in situ hybridization, quantitative real-time PCR, and immunohistochemistry were performed to compare molecular changes among these mice and Ern1 fl/fl and Ern1 fl/fl ;Dspp P19L/+ controls. Western-blotting and stains-all staining analyses support that mutant P19L-DSPP protein was not efficiently secreted into dentin matrix and was accumulated within odontoblasts. Further, immunostaining signals for phosphorylated IRE1α and total XBP1 were dramatically increased in odontoblasts and other dental pulp cells of Dspp P19L/+ and Dspp P19L/P19L mice, in comparison with Dspp +/+ mice. Consistently, there was a small increase in spliced XBP1S protein and Xbp1s mRNA levels in P19L-DSPP mutant mice. Moreover, loss of IRE1α function reduced dentin formation in 2.3 Col1-Cre;Ern1 fl/fl mice and exacerbated the dental defects of P19L-DSPP mutant mice. Notably, IRE1α deficiency did not restore the Dspp mRNA levels in the mutant mice but normalized the increased thickness of the dental pulp chamber floor dentin. These findings underscore the essential role of IRE1α in odontoblast function and dentinogenesis. Moreover, they reveal a context-dependent pathogenic role of IRE1α, providing new insights into ER stress in dental tissue development and disease.
2025-06-05 | Personalized Bonding Approach for Full-Mouth Adhesive Rehabilitation in Dentinogenesis Imperfecta.
Dentinogenesis imperfecta is a rare genetic disorder impacting dentin structure, with an incidence of 1 in 6000 to 1 in 8000 individuals. This condition alters the tooth's color and structure, affecting patients aesthetically, functionally, and socially. Advances in adhesive dentistry offer new therapeutic possibilities, although challenges remain. This article describes the full-mouth adhesive rehabilitation of a 24-year-old male patient diagnosed with DGI, who presented with generalized enamel fractures, shortened crowns, and chronic apical infections. Clinical and radiographic examinations revealed typical features of DGI, including bulbous crowns, short roots, cervical constrictions, and pulpal obliterations. Microscopic analysis of an extracted molar confirmed enamel and dentin structural anomalies, including a smooth dentin-enamel junction (DEJ) and obliterated dentinal tubules. Given the compromised DEJ and high risk of enamel fracture, a minimally invasive, full adhesive treatment plan was developed. The protocol involved resin infiltration (Icon, DMG) to enhance enamel bonding, followed by the placement of lithium disilicate ceramic crowns in the anterior region and monolithic zirconia bridges posteriorly. Vertical dimension of occlusion was increased using composite abutments and a digital workflow ensured accurate, tissue-preserving preparations. The treatment significantly improved the patient's quality of life, with the General Oral Health Assessment Index (GOHAI) increasing from 36/60 to 58/60. A one-year follow-up showed no prosthetic or biological complications. Further research and long-term monitoring are necessary to confirm the clinical stability and effectiveness of this approach in managing dentinogenesis imperfecta.
2021-06-29 | Dentine disorders and adhesive treatments: A systematic review.
A better understanding of the microstructure and mechanical properties of enamel and dentine may enable practitioners to apply the current adhesive dentistry protocols to clinical cases involving dentine disorders (dentinogenesis imperfecta or dentine dysplasia). Publications (up to June 2020) investigating the microstructure of dentine disorders were browsed in a systematic search using the PubMed/Medline, Embase and Cochrane Library electronic databases. Two authors independently selected the studies, extracted the data in accordance with the PRISMA statement, and assessed the risk of bias with the Critical Appraisal Checklist. A Mann-Whitney U test was computed to compare tissues damage related to the two dentine disorders of interest. From an initial total of 642 studies, only 37 (n = 164 teeth) were included in the present analysis, among which 18 investigating enamel (n = 70 teeth), 15 the dentine-enamel junction (n = 62 teeth), and 35 dentine (n = 156 teeth). Dentine is damaged in cases of dentinogenesis imperfecta and osteogenesis imperfecta (p = 2.55E-21 and p = 3.99E-21, respectively). These studies highlight a reduction in mineral density, hardness, modulus of elasticity and abnormal microstructure in dentine disorders. The majority of studies report an altered dentine-enamel junction in dentinogenesis imperfecta and in osteogenesis imperfecta (p = 6.26E-09 and p = 0.001, respectively). Interestingly, enamel is also affected in cases of dentinogenesis imperfecta (p = 0.0013), unlike to osteogenesis imperfecta (p = 0.056). Taking into account all these observations, only a few clinical principles may be favoured in the case of adhesive cementation: (i) to preserve the residual enamel to enhance bonding, (ii) to sandblast the tooth surfaces to increase roughness, (iii) to choose a universal adhesive and reinforce enamel and dentine by means of infiltrant resins. As these recommendations are mostly based on in vitro studies, future in vivo studies should be conducted to confirm these hypotheses.
2019-01-28 | Treatment of an Adolescent Patient with Dentinogenesis Imperfecta Using Indirect Composite Restorations - A Case Report and Literature Review.
To demonstrate the field of application and prospects of individually modeled indirect composite restorations for the treatment of children and adolescents based on a case of dentinogenesis imperfecta. Dental malformations can affect single or multiple teeth. In most cases, direct composite fillings can be placed. However, in severe cases, these restorations may be more challenging and error-prone, especially when occlusal adjustments are necessary. Since composite materials do not require a specific lamination strength and are easy to repair, they can be applied using the indirect technique, enabling conservation of more sound hard tissue than is possible when conventional restorations are used. A young patient with dentinogenesis imperfecta type II underwent interdisciplinary full-mouth rehabilitation due to massive tooth wear and loss of vertical occlusion. First, a check bite was taken, and vertical occlusion was increased using overdentures. Six months later, a construction bite was taken over the existing overdentures (focusing on the sagittal dimension) to move the mandibular position more towards the anterior, correcting the skeletal Class II malocclusion. This resulted in a Class I intercuspidation with harmonization of the facial proportions. After a further six months, all teeth were restored using individually modeled indirect composite restorations, which preserved most of the sound hard tissue and restored esthetics and function. Indirect composite restorations can be a valuable tool for improving occlusion, esthetics and function in the treatment of children and adolescents.
proteins
2023-10-04 | Loss of Bmp2 impairs odontogenesis via dysregulating pAkt/pErk/GCN5/Dlx3/Sp7.
BMP2 signaling plays a pivotal role in odontoblast differentiation and maturation during odontogenesis. Teeth lacking Bmp2 exhibit a morphology reminiscent of dentinogenesis imperfecta (DGI), associated with mutations in dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP) genes. Mechanisms by which BMP2 signaling influences expressions of DSPP and DMP1 and contributes to DGI remain elusive. To study the roles of BMP2 in dentin development, we generated Bmp2 conditional knockout (cKO) mice. Through a comprehensive approach involving RNA-seq, immunohistochemistry, promoter activity, ChIP, and Re-ChIP, we investigated downstream targets of Bmp2. Notably, the absence of Bmp2 in cKO mice led to dentin insufficiency akin to DGI. Disrupted Bmp2 signaling was linked to decreased expression of Dspp and Dmp1, as well as alterations in intracellular translocation of transcription factors Dlx3 and Sp7. Intriguingly, upregulation of Dlx3, Dmp1, Dspp, and Sp7, driven by BMP2, fostered differentiation of dental mesenchymal cells and biomineralization. Mechanistically, BMP2 induced phosphorylation of Dlx3, Sp7, and histone acetyltransferase GCN5 at Thr and Tyr residues, mediated by Akt and Erk42/44 kinases. This phosphorylation facilitated protein nuclear translocation, promoting interactions between Sp7 and Dlx3, as well as with GCN5 on Dspp and Dmp1 promoters. The synergy between Dlx3 and Sp7 bolstered transcription of Dspp and Dmp1. Notably, BMP2-driven GCN5 acetylated Sp7 and histone H3, while also recruiting RNA polymerase II to Dmp1 and Dspp chromatins, enhancing their transcriptions. Intriguingly, BMP2 suppressed the expression of histone deacetylases. we unveil hitherto uncharted involvement of BMP2 in dental cell differentiation and dentine development through pAkt/pErk42/44/Dlx3/Sp7/GCN5/Dspp/Dmp1.
2020-04-30 | Dentinogenesis and Tooth-Alveolar Bone Complex Defects in BMP9/GDF2 Knockout Mice.
Tooth development is regulated by sequential and reciprocal epithelium-mesenchymal interactions and their related molecular signaling pathways, such as bone morphogenetic proteins (BMPs). Among the 14 types of BMPs, BMP9 (also known as growth differentiation factor 2) is one of the most potent BMPs to induce osteogenic differentiation of mesenchymal stem cells. The purpose of this study was to examine potential roles of BMP9 signaling in tooth development. First, we detected the expression pattern of BMP9 in tooth germ during postnatal tooth development, and we found that BMP9 was widely expressed in odontoblasts, ameloblasts, dental pulp cells, and osteoblasts in alveolar bones. Then, we established a BMP9-KO mouse model. Gross morphological examination revealed that the tooth cusps of BMP9-KO mice were significantly abraded with shorter roots. Micro-computed tomography and three-dimensional reconstruction analysis indicated that the first molars of the BMP9-KO mice exhibited a reduced thickness dentin, enlarged pulp canals, and shortened roots, resembling the phenotypes of the common hereditary dental disease dentinogenesis imperfecta. Further, the alveolar bone of the BMP9-KO mutants was found to be shorter and had a decreased mineral density and trabecular thickness and bone volume fraction compared with that of the wild-type control. Mechanistically, we demonstrated that both dentin sialophosphoprotein and dentin matrix protein 1 were induced in dental stem cells by BMP9, whereas their expression was reduced when BMP9 was silenced. Further studies are required to determine whether loss of or decreased BMP9 expression is clinically associated with dentinogenesis imperfecta. Collectively, our results strongly suggest that BMP9 may play an important role in regulating dentinogenesis and tooth development. Further research is recommended into the therapeutic uses of BMP9 to regenerate traumatized and diseased tissues and for the bioengineering of replacement teeth.
2019-06-24 | Bone Morphogenetic Protein 2 Coordinates Early Tooth Mineralization.
Formation of highly organized dental hard tissues is a complex process involving sequential and ordered deposition of an extracellular scaffold, followed by its mineralization. Odontoblast and ameloblast differentiation involves reciprocal and sequential epithelial-mesenchymal interactions. Similar to early tooth development, various Bmps are expressed during this process, although their functions have not been explored in detail. Here, we investigated the role of odontoblast-derived Bmp2 for tooth mineralization using Bmp2 conditional knockout mice. In developing molars, Bmp2LacZ reporter mice revealed restricted expression of Bmp2 in early polarized and functional odontoblasts while it was not expressed in mature odontoblasts. Loss of Bmp2 in neural crest cells, which includes all dental mesenchyme, caused a delay in dentin and enamel deposition. Immunohistochemistry for nestin and dentin sialoprotein (Dsp) revealed polarization defects in odontoblasts, indicative of a role for Bmp2 in odontoblast organization. Surprisingly, pSmad1/5/8, an indicator of Bmp signaling, was predominantly reduced in ameloblasts, with reduced expression of amelogenin ( Amlx), ameloblastin ( Ambn), and matrix metalloproteinase ( Mmp20). Quantitative real-time polymerase chain reaction (RT-qPCR) analysis and immunohistochemistry showed that loss of Bmp2 resulted in increased expression of the Wnt antagonists dickkopf 1 ( Dkk1) in the epithelium and sclerostin ( Sost) in mesenchyme and epithelium. Odontoblasts showed reduced Wnt signaling, which is important for odontoblast differentiation, and a strong reduction in dentin sialophosphoprotein ( Dspp) but not collagen 1 a1 ( Col1a1) expression. Mature Bmp2-deficient teeth, which were obtained by transplanting tooth germs from Bmp2-deficient embryos under a kidney capsule, showed a dentinogenesis imperfecta type II-like appearance. Micro-computed tomography and scanning electron microscopy revealed reduced dentin and enamel thickness, indistinguishable primary and secondary dentin, and deposition of ectopic osteodentin. This establishes that Bmp2 provides an early temporal, nonredundant signal for directed and organized tooth mineralization.
2017-12-20 | Transgenic expression of Dspp partially rescued the long bone defects of Dmp1-null mice.
Dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP) belong to the Small Integrin-Binding Ligand N-linked Glycoprotein (SIBLING) family. In addition to the features common to all SIBLING members, DMP1 and DSPP share several unique similarities in chemical structure, proteolytic activation and tissue localization. Mutations in, or deletion of DMP1, cause autosomal recessive hypophosphatemic rickets along with dental defects; DSPP mutations or its ablation are associated with dentinogenesis imperfecta. While the roles and functional mechanisms of DMP1 in osteogenesis have been extensively studied, those of DSPP in long bones have been studied only to a limited extent. Previous studies by our group revealed that transgenic expression of Dspp completely rescued the dentin defects of Dmp1-null (Dmp1(-/-)) mice. In this investigation, we assessed the effects of transgenic Dspp on osteogenesis by analyzing the formation and mineralization of the long bones in Dmp1(-/-) mice that expresses a transgene encoding full-length DSPP driven by a 3.6-kb rat Col1a1 promoter (referred as "Dmp1(-/-);Dspp-Tg mice"). We characterized the long bones of the Dmp1(-/-);Dspp-Tg mice at different ages and compared them with those from Dmp1(-/-) and Dmp1(+/-) (normal control) mice. Our analyses showed that the long bones of Dmp1(-/-);Dspp-Tg mice had a significant increase in cortical bone thickness, bone volume and mineral density along with a remarkable restoration of trabecular thickness compared to those of the Dmp1(-/-) mice. The long bones of Dmp1(-/-);Dspp-Tg mice underwent a dramatic reduction in the amount of osteoid, significant improvement of the collagen fibrillar network, and better organization of the lacunocanalicular system, compared to the Dmp1(-/-) mice. The elevated levels of biglycan, bone sialoprotein and osteopontin in Dmp1(-/-) mice were also noticeably corrected by the transgenic expression of Dspp. These findings suggest that DSPP and DMP1 may function synergistically within the complex milieus of bone matrices.
2015-10-13 | Establishment of Immortalized Mouse Bmp2 Knock-Out Dental Papilla Mesenchymal Cells Necessary for Study of Odontoblastic Differentiation and Odontogenesis.
Bmp2 is essential for dentin formation. Bmp2 cKO mice exhibited similar phenotype to dentinogenesis imperfecta, showing dental pulp exposure, hypomineralized dentin, and delayed odontoblast differentiation. As it is relatively difficult to obtain lot of primary Bmp2 cKO dental papilla mesenchymal cells and to maintain a long-term culture of these primary cells, availability of immortalized deleted Bmp2 dental papilla mesenchymal cells is critical for studying the underlying mechanism of Bmp2 signal in odontogenesis. In this study, our goal was to generate an immortalized deleted Bmp2 dental papilla mesenchymal (iBmp2(ko/ko)dp) cell line by introducing Cre recombinase and green fluorescent protein (GFP) into the immortalized mouse floxed Bmp2 dental papilla mesenchymal (iBmp2(fx/fx)dp) cells. iBmp2(ko/ko)dp cells were confirmed by GFP and PCR. The deleted Bmp2 cells exhibited slow cell proliferation rate and cell growth was arrested in G2 phase. Expression of tooth-related marker genes and cell differentiation were decreased in the deleted cells. Importantly, extracellular matrix remodeling was impaired in the iBmp2(ko/ko)dp cells as reflected by the decreased Mmp-9 expression. In addition, with exogenous Bmp2 induction, these cell differentiation and mineralization were rescued as well as extracellular matrix remodeling was enhanced. Therefore, we for the first time described establishment of iBmp(ko/ko) cells that are useful for study of mechanisms in regulating dental papilla mesenchymal cell lineages.
cell therapies
2025-08-12 | Guided Endodontics in Managing Root Canal Treatment for Anomalous Teeth-A Narrative Review.
This review evaluates the effectiveness and clinical applicability of guided endodontics (GE) in managing dental anomalies, which present challenges for conventional endodontics. The primary objective is to assess how GE enhances treatment predictability and minimises errors in cases such as dens invaginatus (DI), dentinogenesis imperfecta (DGI), dentinal dysplasia (DD), dens evaginatus (DE) and dental fusion. A narrative review was conducted using a comprehensive search across PubMed/MEDLINE, Scopus, Web of Science, EMBASE and Cochrane Library databases for studies published 2015-2025. Nine studies met the inclusion criteria. GE was found to offer high success rates in the treatment of DI, DGI and DD. The integration of CBCT and 3D-printed guides allowed for minimally invasive access cavity preparation, reduced iatrogenic complications and improved precision. Despite these advantages, challenges include increased cost, being time-consuming and limitations in curved canals. Guided endodontics holds promise as a transformative technique in modern endodontic practice.
2024-10-29 | Endodontic Management of Dentinogenesis Imperfecta Using Guided Endodontics: A Case Report.
Pulp canal calcification (PCC) is common in patients with dentinogenesis imperfecta (DGI). We present endodontic management of multiple anterior and posterior teeth with PCCs in a patient with DGI type II using guided endodontics. A 26-year-old female patient was diagnosed with DGI type II. Clinical examination revealed palatal cusp fracture in tooth #13, microcracks in tooth #14, and a sinus tract in the maxillary right buccal vestibule related to tooth #13. Periapical radiographs revealed PCCs in all teeth, and periapical radiolucencies in several teeth. Due to difficult negotiation of canal orifices, guided endodontic approach was planned. Cone-beam computed tomography (CBCT) was requested and obtained. Intraoral scanning was performed, and CBCT and intraoral scanning data were superimposed. A template was designed and 3D printed. The root canal orifices were successfully negotiated and endodontic treatments were successfully accomplished. At the 1-year follow-up, the endodontically treated teeth were asymptomatic, and periapical lesions were healing.
2024-01-15 | Regenerative Endodontic Treatment in Dentinogenesis Imperfecta-Induced Apical Periodontitis.
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.
small molecules
2026-03-07 | Calcium phosphate polymer induced liquid precursor improves dentin bonding performance of primary teeth with dentinogenesis imperfecta type II.
OBJECTIVES: The current study aims to assess the dentin bonding performance of primary molars with dentinogenesis imperfecta type II (DGI-II). Moreover, we assess the efficacy of calcium phosphate polymer induced liquid precursor (Ca/P-PILP), a biomimetic remineralization material, in improving the resin bonding performance of DGI-II dentin. MATERIALS AND METHODS: Dentin specimens from normal and DGI-II primary molars were treated with either Ca/P-PILP or double-distilled water. Morphology of these dentin specimens were observed using scanning electron microscopy (SEM), and the calcium and phosphorus contents were determined by energy-dispersive X-ray spectroscopy (EDS). Micro-tensile bond strength (µTBS) analysis was conducted to evaluate the resin bonding strength of dentin. RESULTS: SEM results showed that compared with normal dentin, DGI-II dentin exhibited significantly fewer dentinal tubules with nearly no intact tubular structures. Meanwhile, the dentin collagen fibers exhibited disorganized arrangement and compromised structural integrity. Compared with normal dentin, DGI-II dentin displayed inferior bonding performance with resin as shown by µTBS analysis, and EDS analyses showed that DGI-II dentin contained lower calcium and phosphorus contents. After treatment with Ca/P-PILP, the calcium and phosphorus contents of DGI-II dentin were significantly increased as shown by EDS analyses, and µTBS analysis showed that the bonding performance of DGI-II dentin was improved, while no notable effect was observed in normal dentin. CONCLUSIONS: Primary molars with DGI-II display structural defects and reduced calcium and phosphorus contents in dentin. The reduced mineral contents are partially responsible for the compromised bonding performance of DGI-II dentin, for Ca/P-PILP which effectively enhances the mineral contents of DGI-II dentin improves the resin bonding performance of DGI-II dentin.
2025-12-24 | Inositol-requiring enzyme 1 alpha is essential for dentinogenesis.
Inositol-requiring enzyme 1 alpha (IRE1α), encoded by endoplasmic reticulum (ER) to nucleus signaling 1 (Ern1) gene, is the most conserved sensor of ER stress. IRE1α-initiated signaling pathways contribute to functional maturation of secretory cells and have been implicated in various human diseases. In this study, we examined the roles of IRE1α in odontoblast development and dentin formation in wild-type mice as well as in Dspp P19L mutant mice, which express a pathogenic variant of dentin sialophosphoprotein (P19L-DSPP) and exhibit a dentinogenesis imperfecta (DGI)-like phenotype. Western-blotting and stains-all staining analyses were used to assess whether secretion of mutant P19L-DSPP was impaired in dental pulp cells containing odontoblasts from Dspp P19L/P19L mice compared with Dspp +/+ controls. Immunohistochemistry and reverse-transcription PCR were performed to examine changes in IRE1α and its downstream target X-box binding protein 1 (XBP1) in P19L-DSPP mutant mice. To further investigate the roles of IRE1α in tooth development, we generated 2.3 Col1-Cre;Ern1 fl/fl and compound 2.3 Col1-Cre;Ern1 fl/fl ;Dspp P19L/+ mice. Structural and histological changes in mandibular molars were analyzed using plain X-ray radiography, micro-computed tomography (µCT), and histology. Additionally, in situ hybridization, quantitative real-time PCR, and immunohistochemistry were performed to compare molecular changes among these mice and Ern1 fl/fl and Ern1 fl/fl ;Dspp P19L/+ controls. Western-blotting and stains-all staining analyses support that mutant P19L-DSPP protein was not efficiently secreted into dentin matrix and was accumulated within odontoblasts. Further, immunostaining signals for phosphorylated IRE1α and total XBP1 were dramatically increased in odontoblasts and other dental pulp cells of Dspp P19L/+ and Dspp P19L/P19L mice, in comparison with Dspp +/+ mice. Consistently, there was a small increase in spliced XBP1S protein and Xbp1s mRNA levels in P19L-DSPP mutant mice. Moreover, loss of IRE1α function reduced dentin formation in 2.3 Col1-Cre;Ern1 fl/fl mice and exacerbated the dental defects of P19L-DSPP mutant mice. Notably, IRE1α deficiency did not restore the Dspp mRNA levels in the mutant mice but normalized the increased thickness of the dental pulp chamber floor dentin. These findings underscore the essential role of IRE1α in odontoblast function and dentinogenesis. Moreover, they reveal a context-dependent pathogenic role of IRE1α, providing new insights into ER stress in dental tissue development and disease.
2025-06-05 | Personalized Bonding Approach for Full-Mouth Adhesive Rehabilitation in Dentinogenesis Imperfecta.
Dentinogenesis imperfecta is a rare genetic disorder impacting dentin structure, with an incidence of 1 in 6000 to 1 in 8000 individuals. This condition alters the tooth's color and structure, affecting patients aesthetically, functionally, and socially. Advances in adhesive dentistry offer new therapeutic possibilities, although challenges remain. This article describes the full-mouth adhesive rehabilitation of a 24-year-old male patient diagnosed with DGI, who presented with generalized enamel fractures, shortened crowns, and chronic apical infections. Clinical and radiographic examinations revealed typical features of DGI, including bulbous crowns, short roots, cervical constrictions, and pulpal obliterations. Microscopic analysis of an extracted molar confirmed enamel and dentin structural anomalies, including a smooth dentin-enamel junction (DEJ) and obliterated dentinal tubules. Given the compromised DEJ and high risk of enamel fracture, a minimally invasive, full adhesive treatment plan was developed. The protocol involved resin infiltration (Icon, DMG) to enhance enamel bonding, followed by the placement of lithium disilicate ceramic crowns in the anterior region and monolithic zirconia bridges posteriorly. Vertical dimension of occlusion was increased using composite abutments and a digital workflow ensured accurate, tissue-preserving preparations. The treatment significantly improved the patient's quality of life, with the General Oral Health Assessment Index (GOHAI) increasing from 36/60 to 58/60. A one-year follow-up showed no prosthetic or biological complications. Further research and long-term monitoring are necessary to confirm the clinical stability and effectiveness of this approach in managing dentinogenesis imperfecta.
2021-06-29 | Dentine disorders and adhesive treatments: A systematic review.
A better understanding of the microstructure and mechanical properties of enamel and dentine may enable practitioners to apply the current adhesive dentistry protocols to clinical cases involving dentine disorders (dentinogenesis imperfecta or dentine dysplasia). Publications (up to June 2020) investigating the microstructure of dentine disorders were browsed in a systematic search using the PubMed/Medline, Embase and Cochrane Library electronic databases. Two authors independently selected the studies, extracted the data in accordance with the PRISMA statement, and assessed the risk of bias with the Critical Appraisal Checklist. A Mann-Whitney U test was computed to compare tissues damage related to the two dentine disorders of interest. From an initial total of 642 studies, only 37 (n = 164 teeth) were included in the present analysis, among which 18 investigating enamel (n = 70 teeth), 15 the dentine-enamel junction (n = 62 teeth), and 35 dentine (n = 156 teeth). Dentine is damaged in cases of dentinogenesis imperfecta and osteogenesis imperfecta (p = 2.55E-21 and p = 3.99E-21, respectively). These studies highlight a reduction in mineral density, hardness, modulus of elasticity and abnormal microstructure in dentine disorders. The majority of studies report an altered dentine-enamel junction in dentinogenesis imperfecta and in osteogenesis imperfecta (p = 6.26E-09 and p = 0.001, respectively). Interestingly, enamel is also affected in cases of dentinogenesis imperfecta (p = 0.0013), unlike to osteogenesis imperfecta (p = 0.056). Taking into account all these observations, only a few clinical principles may be favoured in the case of adhesive cementation: (i) to preserve the residual enamel to enhance bonding, (ii) to sandblast the tooth surfaces to increase roughness, (iii) to choose a universal adhesive and reinforce enamel and dentine by means of infiltrant resins. As these recommendations are mostly based on in vitro studies, future in vivo studies should be conducted to confirm these hypotheses.
2019-01-28 | Treatment of an Adolescent Patient with Dentinogenesis Imperfecta Using Indirect Composite Restorations - A Case Report and Literature Review.
To demonstrate the field of application and prospects of individually modeled indirect composite restorations for the treatment of children and adolescents based on a case of dentinogenesis imperfecta. Dental malformations can affect single or multiple teeth. In most cases, direct composite fillings can be placed. However, in severe cases, these restorations may be more challenging and error-prone, especially when occlusal adjustments are necessary. Since composite materials do not require a specific lamination strength and are easy to repair, they can be applied using the indirect technique, enabling conservation of more sound hard tissue than is possible when conventional restorations are used. A young patient with dentinogenesis imperfecta type II underwent interdisciplinary full-mouth rehabilitation due to massive tooth wear and loss of vertical occlusion. First, a check bite was taken, and vertical occlusion was increased using overdentures. Six months later, a construction bite was taken over the existing overdentures (focusing on the sagittal dimension) to move the mandibular position more towards the anterior, correcting the skeletal Class II malocclusion. This resulted in a Class I intercuspidation with harmonization of the facial proportions. After a further six months, all teeth were restored using individually modeled indirect composite restorations, which preserved most of the sound hard tissue and restored esthetics and function. Indirect composite restorations can be a valuable tool for improving occlusion, esthetics and function in the treatment of children and adolescents.
proteins
2023-10-04 | Loss of Bmp2 impairs odontogenesis via dysregulating pAkt/pErk/GCN5/Dlx3/Sp7.
BMP2 signaling plays a pivotal role in odontoblast differentiation and maturation during odontogenesis. Teeth lacking Bmp2 exhibit a morphology reminiscent of dentinogenesis imperfecta (DGI), associated with mutations in dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP) genes. Mechanisms by which BMP2 signaling influences expressions of DSPP and DMP1 and contributes to DGI remain elusive. To study the roles of BMP2 in dentin development, we generated Bmp2 conditional knockout (cKO) mice. Through a comprehensive approach involving RNA-seq, immunohistochemistry, promoter activity, ChIP, and Re-ChIP, we investigated downstream targets of Bmp2. Notably, the absence of Bmp2 in cKO mice led to dentin insufficiency akin to DGI. Disrupted Bmp2 signaling was linked to decreased expression of Dspp and Dmp1, as well as alterations in intracellular translocation of transcription factors Dlx3 and Sp7. Intriguingly, upregulation of Dlx3, Dmp1, Dspp, and Sp7, driven by BMP2, fostered differentiation of dental mesenchymal cells and biomineralization. Mechanistically, BMP2 induced phosphorylation of Dlx3, Sp7, and histone acetyltransferase GCN5 at Thr and Tyr residues, mediated by Akt and Erk42/44 kinases. This phosphorylation facilitated protein nuclear translocation, promoting interactions between Sp7 and Dlx3, as well as with GCN5 on Dspp and Dmp1 promoters. The synergy between Dlx3 and Sp7 bolstered transcription of Dspp and Dmp1. Notably, BMP2-driven GCN5 acetylated Sp7 and histone H3, while also recruiting RNA polymerase II to Dmp1 and Dspp chromatins, enhancing their transcriptions. Intriguingly, BMP2 suppressed the expression of histone deacetylases. we unveil hitherto uncharted involvement of BMP2 in dental cell differentiation and dentine development through pAkt/pErk42/44/Dlx3/Sp7/GCN5/Dspp/Dmp1.
2020-04-30 | Dentinogenesis and Tooth-Alveolar Bone Complex Defects in BMP9/GDF2 Knockout Mice.
Tooth development is regulated by sequential and reciprocal epithelium-mesenchymal interactions and their related molecular signaling pathways, such as bone morphogenetic proteins (BMPs). Among the 14 types of BMPs, BMP9 (also known as growth differentiation factor 2) is one of the most potent BMPs to induce osteogenic differentiation of mesenchymal stem cells. The purpose of this study was to examine potential roles of BMP9 signaling in tooth development. First, we detected the expression pattern of BMP9 in tooth germ during postnatal tooth development, and we found that BMP9 was widely expressed in odontoblasts, ameloblasts, dental pulp cells, and osteoblasts in alveolar bones. Then, we established a BMP9-KO mouse model. Gross morphological examination revealed that the tooth cusps of BMP9-KO mice were significantly abraded with shorter roots. Micro-computed tomography and three-dimensional reconstruction analysis indicated that the first molars of the BMP9-KO mice exhibited a reduced thickness dentin, enlarged pulp canals, and shortened roots, resembling the phenotypes of the common hereditary dental disease dentinogenesis imperfecta. Further, the alveolar bone of the BMP9-KO mutants was found to be shorter and had a decreased mineral density and trabecular thickness and bone volume fraction compared with that of the wild-type control. Mechanistically, we demonstrated that both dentin sialophosphoprotein and dentin matrix protein 1 were induced in dental stem cells by BMP9, whereas their expression was reduced when BMP9 was silenced. Further studies are required to determine whether loss of or decreased BMP9 expression is clinically associated with dentinogenesis imperfecta. Collectively, our results strongly suggest that BMP9 may play an important role in regulating dentinogenesis and tooth development. Further research is recommended into the therapeutic uses of BMP9 to regenerate traumatized and diseased tissues and for the bioengineering of replacement teeth.
2019-06-24 | Bone Morphogenetic Protein 2 Coordinates Early Tooth Mineralization.
Formation of highly organized dental hard tissues is a complex process involving sequential and ordered deposition of an extracellular scaffold, followed by its mineralization. Odontoblast and ameloblast differentiation involves reciprocal and sequential epithelial-mesenchymal interactions. Similar to early tooth development, various Bmps are expressed during this process, although their functions have not been explored in detail. Here, we investigated the role of odontoblast-derived Bmp2 for tooth mineralization using Bmp2 conditional knockout mice. In developing molars, Bmp2LacZ reporter mice revealed restricted expression of Bmp2 in early polarized and functional odontoblasts while it was not expressed in mature odontoblasts. Loss of Bmp2 in neural crest cells, which includes all dental mesenchyme, caused a delay in dentin and enamel deposition. Immunohistochemistry for nestin and dentin sialoprotein (Dsp) revealed polarization defects in odontoblasts, indicative of a role for Bmp2 in odontoblast organization. Surprisingly, pSmad1/5/8, an indicator of Bmp signaling, was predominantly reduced in ameloblasts, with reduced expression of amelogenin ( Amlx), ameloblastin ( Ambn), and matrix metalloproteinase ( Mmp20). Quantitative real-time polymerase chain reaction (RT-qPCR) analysis and immunohistochemistry showed that loss of Bmp2 resulted in increased expression of the Wnt antagonists dickkopf 1 ( Dkk1) in the epithelium and sclerostin ( Sost) in mesenchyme and epithelium. Odontoblasts showed reduced Wnt signaling, which is important for odontoblast differentiation, and a strong reduction in dentin sialophosphoprotein ( Dspp) but not collagen 1 a1 ( Col1a1) expression. Mature Bmp2-deficient teeth, which were obtained by transplanting tooth germs from Bmp2-deficient embryos under a kidney capsule, showed a dentinogenesis imperfecta type II-like appearance. Micro-computed tomography and scanning electron microscopy revealed reduced dentin and enamel thickness, indistinguishable primary and secondary dentin, and deposition of ectopic osteodentin. This establishes that Bmp2 provides an early temporal, nonredundant signal for directed and organized tooth mineralization.
2017-12-20 | Transgenic expression of Dspp partially rescued the long bone defects of Dmp1-null mice.
Dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP) belong to the Small Integrin-Binding Ligand N-linked Glycoprotein (SIBLING) family. In addition to the features common to all SIBLING members, DMP1 and DSPP share several unique similarities in chemical structure, proteolytic activation and tissue localization. Mutations in, or deletion of DMP1, cause autosomal recessive hypophosphatemic rickets along with dental defects; DSPP mutations or its ablation are associated with dentinogenesis imperfecta. While the roles and functional mechanisms of DMP1 in osteogenesis have been extensively studied, those of DSPP in long bones have been studied only to a limited extent. Previous studies by our group revealed that transgenic expression of Dspp completely rescued the dentin defects of Dmp1-null (Dmp1(-/-)) mice. In this investigation, we assessed the effects of transgenic Dspp on osteogenesis by analyzing the formation and mineralization of the long bones in Dmp1(-/-) mice that expresses a transgene encoding full-length DSPP driven by a 3.6-kb rat Col1a1 promoter (referred as "Dmp1(-/-);Dspp-Tg mice"). We characterized the long bones of the Dmp1(-/-);Dspp-Tg mice at different ages and compared them with those from Dmp1(-/-) and Dmp1(+/-) (normal control) mice. Our analyses showed that the long bones of Dmp1(-/-);Dspp-Tg mice had a significant increase in cortical bone thickness, bone volume and mineral density along with a remarkable restoration of trabecular thickness compared to those of the Dmp1(-/-) mice. The long bones of Dmp1(-/-);Dspp-Tg mice underwent a dramatic reduction in the amount of osteoid, significant improvement of the collagen fibrillar network, and better organization of the lacunocanalicular system, compared to the Dmp1(-/-) mice. The elevated levels of biglycan, bone sialoprotein and osteopontin in Dmp1(-/-) mice were also noticeably corrected by the transgenic expression of Dspp. These findings suggest that DSPP and DMP1 may function synergistically within the complex milieus of bone matrices.
2015-10-13 | Establishment of Immortalized Mouse Bmp2 Knock-Out Dental Papilla Mesenchymal Cells Necessary for Study of Odontoblastic Differentiation and Odontogenesis.
Bmp2 is essential for dentin formation. Bmp2 cKO mice exhibited similar phenotype to dentinogenesis imperfecta, showing dental pulp exposure, hypomineralized dentin, and delayed odontoblast differentiation. As it is relatively difficult to obtain lot of primary Bmp2 cKO dental papilla mesenchymal cells and to maintain a long-term culture of these primary cells, availability of immortalized deleted Bmp2 dental papilla mesenchymal cells is critical for studying the underlying mechanism of Bmp2 signal in odontogenesis. In this study, our goal was to generate an immortalized deleted Bmp2 dental papilla mesenchymal (iBmp2(ko/ko)dp) cell line by introducing Cre recombinase and green fluorescent protein (GFP) into the immortalized mouse floxed Bmp2 dental papilla mesenchymal (iBmp2(fx/fx)dp) cells. iBmp2(ko/ko)dp cells were confirmed by GFP and PCR. The deleted Bmp2 cells exhibited slow cell proliferation rate and cell growth was arrested in G2 phase. Expression of tooth-related marker genes and cell differentiation were decreased in the deleted cells. Importantly, extracellular matrix remodeling was impaired in the iBmp2(ko/ko)dp cells as reflected by the decreased Mmp-9 expression. In addition, with exogenous Bmp2 induction, these cell differentiation and mineralization were rescued as well as extracellular matrix remodeling was enhanced. Therefore, we for the first time described establishment of iBmp(ko/ko) cells that are useful for study of mechanisms in regulating dental papilla mesenchymal cell lineages.
cell therapies
2025-08-12 | Guided Endodontics in Managing Root Canal Treatment for Anomalous Teeth-A Narrative Review.
This review evaluates the effectiveness and clinical applicability of guided endodontics (GE) in managing dental anomalies, which present challenges for conventional endodontics. The primary objective is to assess how GE enhances treatment predictability and minimises errors in cases such as dens invaginatus (DI), dentinogenesis imperfecta (DGI), dentinal dysplasia (DD), dens evaginatus (DE) and dental fusion. A narrative review was conducted using a comprehensive search across PubMed/MEDLINE, Scopus, Web of Science, EMBASE and Cochrane Library databases for studies published 2015-2025. Nine studies met the inclusion criteria. GE was found to offer high success rates in the treatment of DI, DGI and DD. The integration of CBCT and 3D-printed guides allowed for minimally invasive access cavity preparation, reduced iatrogenic complications and improved precision. Despite these advantages, challenges include increased cost, being time-consuming and limitations in curved canals. Guided endodontics holds promise as a transformative technique in modern endodontic practice.
2024-10-29 | Endodontic Management of Dentinogenesis Imperfecta Using Guided Endodontics: A Case Report.
Pulp canal calcification (PCC) is common in patients with dentinogenesis imperfecta (DGI). We present endodontic management of multiple anterior and posterior teeth with PCCs in a patient with DGI type II using guided endodontics. A 26-year-old female patient was diagnosed with DGI type II. Clinical examination revealed palatal cusp fracture in tooth #13, microcracks in tooth #14, and a sinus tract in the maxillary right buccal vestibule related to tooth #13. Periapical radiographs revealed PCCs in all teeth, and periapical radiolucencies in several teeth. Due to difficult negotiation of canal orifices, guided endodontic approach was planned. Cone-beam computed tomography (CBCT) was requested and obtained. Intraoral scanning was performed, and CBCT and intraoral scanning data were superimposed. A template was designed and 3D printed. The root canal orifices were successfully negotiated and endodontic treatments were successfully accomplished. At the 1-year follow-up, the endodontically treated teeth were asymptomatic, and periapical lesions were healing.
2024-01-15 | Regenerative Endodontic Treatment in Dentinogenesis Imperfecta-Induced Apical Periodontitis.
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.
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