Dentin Dysplasia Type Research Articles

Clinical features and causative genes of dentin dysplasia type Ⅰ with a 13-year follow-up

Clinical features and causative genes of dentin dysplasia type Ⅰ with a 13-year follow-up

Recognition on dentin dysplasia type Ⅱ

Dentin dysplasia type Ⅱ (DD-Ⅱ) is a subtype of hereditary dentin disorders. The dentin sialophosphoprotein (DSPP) gene has been revealed to be the causative gene, whose mutations could affect the normal tooth development process. The lesions involve both deciduous and permanent dentition, mainly manifested as tooth discoloration, attrition and even the subsequent malocclusion. If not treated in time, it will significantly affect the physical and psychological health of patients. The disease is difficult to be diagnosed in clinic accurately as its low incidence and hidden manifestations. The present article aims to discuss the clinical and radiographic characteristics, diagnosis, treatment of DD-Ⅱ, in order to improve the overall understanding on DD-Ⅱ for clinicians.

Progress in the classification of hereditary dentin disorders and clinical management strategies

Heterogeneous mutations in dentin sialophosphoprotein (DSPP) gene, which is located on autosome 4, are associated with hereditary dentin developmental disorders. According to the new classification proposed by de La Dure-Molla et al, diseases caused by DSPP gene mutations mainly manifested as abnormal dentin development are collectively referred to as dentinogenesis imperfecta (DI), including dentin dysplasia type Ⅱ (DD-Ⅱ), dentinogenesis imperfecta type Ⅱ (DGI-Ⅱ) and dentinogenesis imperfecta type Ⅲ (DGI-Ⅲ) in Shields classification. And dentin dysplasia type Ⅰ (DD-Ⅰ) in Shields classification is redesignated as radicular dentin dysplasia. In this paper, progress in the classification, clinical characteristics and genetic mechanisms of DI are reviewed. This paper also provides clinical management and treatment strategies for patients suffering DI.

A novel DSPP frameshift mutation causing dentin dysplasia type 2 and disease management strategies.

The present study aims to investigate the mutation in a Chinese family with dentin dysplasia type II (DD-II) and to summarize mutation hotspots, clinical manifestations, and disease management strategies. Phenotype analysis, clinical intervention, mutation screening, and cosegregation analysis within the enrolled family were performed. A summary of the reported mutations in the dentin phosphoprotein (DPP) region of dentin sialophosphoprotein (DSPP) was analyzed. Pathogenicity prediction analysis of the physical properties and function of DSPP variants was performed by bioinformatic processing. Clinical management strategies are discussed. A novel pathogenic mutation (c.2035delA) in the DPP region of DSPP was identified, which was cosegregated in the family. The immature permanent teeth of patients with DD-II presented with X-shaped root canal phenotypes. Most of the identified mutations for DD-II were clustered in the DPP region between nucleotides 1686-2134. Points of differential diagnosis, clinical interventions, and management strategies are proposed. This study revealed a novel DSPP frameshift mutation and presented new clinical features of DD-II. The locus involving nucleotides 1686-2134 of DSPP may represent a mutational hotspot for the disease. Appropriate management of DD-II at different stages is important to avoid the development of secondary dental lesions.

Mutation of dentin sialophosphoprotein and hereditary malformations of dentin

The classification as well as the clinical manifestations of hereditary malformations of dentin are of great concern and have been deeply elucidated. The understanding of its genetic basis also increases progressively. Dentin sialophosphoprotein (DSPP) is the pathogenic gene of dentinogenesis imperfecta type Ⅱ, dentinogenesis imperfecta type Ⅲ and dentin dysplasia type Ⅱ. In this article, the classification of DSPP mutations as well as the resultant dysfunction of the mutant DSPP are summarized respectively and the corresponding clinical manifestations are analyzed. This work will provide a reference for the diagnosis and treatment of hereditary malformations of dentin.

Withdrawal: A novel DSPP frameshift mutation causing dentin dysplasia type 2 and disease management strategies.

To investigate the mutation in two Chinese families with dentin dysplasia type II (DD-II) and to summarize mutation hotspots, clinical manifestations, and disease management strategies. Phenotype analysis, clinical intervention, mutation screening, and co-segregation analysis within the enrolled families were performed. A summary of the reported mutations in the dentin phosphoprotein (DPP) region of dentin sialophosphoprotein (DSPP) was analysed. Pathogenicity prediction analysis of the physical properties and function of DSPP variants were performed by bioinformatic processing. Clinical management strategies are discussed. A novel pathogenic mutation (c.2035delA) in the DPP region of DSPP was identified, which was co-segregated in the families of patients. The immature permanent teeth of patients with DD-II presented with X-shaped root canal phenotypes. Most of the identified mutations for DD-II were clustered in the DPP region between nucleotides 1686-2134. Points of differential diagnosis, clinical interventions, and management strategies are proposed. This study revealed a novel DSPP frameshift mutation and presented new clinical features of DD-II. The locus involving nucleotides 1686-2134 of DSPP may represent a mutational hotspot for the disease. Appropriate management of DD-II at different stages is important to avoid the development of secondary dental lesions.

Translated Mutant DSPP mRNA Expression Level Impacts the Severity of Dentin Defects.

Hereditary dentin defects are conventionally classified into three types of dentinogenesis imperfecta (DGI) and two types of dentin dysplasia (DD). Mutations in the dentin sialophosphoprotein (DSPP) gene have been identified to cause DGI type II and III and DD type II; therefore, these are not three different conditions, but rather allelic disorders. In this study, we recruited three families with varying clinical phenotypes from DGI-III to DD-II and performed mutational analysis by candidate gene analysis or whole-exome sequencing. Three novel mutations including a silent mutation (NM_014208.3: c.52-2del, c.135+1G>C, and c.135G>A; p.(Gln45=)) were identified, all of which affected pre-mRNA splicing. Comparison of the splicing assay results revealed that the expression level of the DSPP exon 3 deletion transcript correlated with the severity of the dentin defects. This study did not only expand the mutational spectrum of DSPP gene, but also advanced our understanding of the molecular pathogenesis impacting the severity of hereditary dentin defects.

Micro-CT study on isolated teeth with hereditary dentin defects.

To construct the three-dimensional structure of the isolated teeth of patients with dentinogenesis imperfecta type Ⅱ (DGI-Ⅱ) and dentin dysplasia type Ⅰ (DD-Ⅰ) by using Micro-CT and explore internal structure and hard tissue mineralization density. The three-dimensional structures of the third molars collected from patients with DGI-Ⅱ and DD-Ⅰ and healthy individuals of the same age were reconstructed by using Micro-CT (Mimics 17.0). The internal structures of the affected teeth along the sagittal and transverse planes were observed. The grayscale values of the enamel, crown dentin, and root dentin were calculated. Then, the mineralization densities of the different parts of the teeth of the three groups were analyzed. The detailed three-dimensional models of the mandibular third molars with hereditary dentin defects were successfully constructed. The models contained the models of the enamel cap, dentin core, and pulp cavity. Sagittal and transverse section scans revealed that in patients with DGI-Ⅱ, the pulp cavity was incompletely calcified and the root canal was narrow, whereas in those with DD-Ⅰ, the pulp cavity and root canal were obliterated and the root of the tooth was absent. The analysis of the grayscale values showed that compared with those in the healthy group, the grayscale values of the enamel, crown dentin, and root dentin were lower in the DGI-Ⅱ and DD-Ⅰ groups (P<0.01). No significant differences in the grayscale values of the enamel and crown dentin were found between the DGI-Ⅱ and DD-Ⅰ groups (P>0.05), whereas the grayscale value of the root dentin showed statistically significant differences between the two groups (P<0.01). The application of Micro-CT provided a simple and accurate method for the three-dimensional structure reconstruction and quantitative analysis of the mineralization density of isolated teeth with hereditary dentin defects. Although the dentin mineralization density of DGI-Ⅱ and DD-Ⅰ teeth decreased, the decrement shown by DD-Ⅰ teeth was more significant than that shown by DGI-Ⅱ teeth. The pulp cavity had abnormal calcifications, and the root canal was narrow or even occluded.

The critical role of nuclear factor I-C in tooth development.

Nuclear factor I-C (NFIC) plays a critical role in regulating epithelial-mesenchymal crosstalk during tooth development. However, it remains largely unknown about how NFIC functions in dentin and enamel formation. In the present review, we aim to summarize the most recent discoveries in the field and gain a better understanding of the roles NFIC performs during tooth formation. Nfic-/- mice exhibit human dentin dysplasia type I (DDI)-like phenotypes signified by enlarged pulp chambers, the presence of short-root anomaly, and failure of odontoblast differentiation. Although loss of NFIC has little effect on molar crown morphology, researchers have detected aberrant microstructures of enamel in the incisors. Recently, accumulating evidence has further uncovered the novel function of NFIC in the process of enamel and dentin formation. During epithelial-mesenchyme crosstalk, the expression of NFIC is under the control of SHH-PTCH-SMO-GLI1 pathway. NFIC is closely involved in odontoblast lineage cells proliferation and differentiation, and the maintenance of NFIC protein level in cytoplasm is negatively regulated by TGF-β signaling pathway. In addition, NFIC has mild effect on ameloblast differentiation, enamel mineralization and cementum formation. NFIC plays an important role in tooth development and is required for the formation of dentin, enamel as well as cementum.

Mouse Dspp frameshift model of human dentinogenesis imperfecta

Non-syndromic inherited defects of tooth dentin are caused by two classes of dominant negative/gain-of-function mutations in dentin sialophosphoprotein (DSPP): 5′ mutations affecting an N-terminal targeting sequence and 3′ mutations that shift translation into the − 1 reading frame. DSPP defects cause an overlapping spectrum of phenotypes classified as dentin dysplasia type II and dentinogenesis imperfecta types II and III. Using CRISPR/Cas9, we generated a Dspp−1fs mouse model by introducing a FLAG-tag followed by a single nucleotide deletion that translated 493 extraneous amino acids before termination. Developing incisors and/or molars from this mouse and a DsppP19L mouse were characterized by morphological assessment, bSEM, nanohardness testing, histological analysis, in situ hybridization and immunohistochemistry. DsppP19L dentin contained dentinal tubules but grew slowly and was softer and less mineralized than the wild-type. DsppP19L incisor enamel was softer than normal, while molar enamel showed reduced rod/interrod definition. Dspp−1fs dentin formation was analogous to reparative dentin: it lacked dentinal tubules, contained cellular debris, and was significantly softer and thinner than Dspp+/+ and DsppP19L dentin. The Dspp−1fs incisor enamel appeared normal and was comparable to the wild-type in hardness. We conclude that 5′ and 3′ Dspp mutations cause dental malformations through different pathological mechanisms and can be regarded as distinct disorders.

CLINICAL CASE OF DENTINE DYSPLASIA TYPE I

Developmental dental hard tissues disorders are rarely diagnosed both in children and adults, and their treatment is a problem for dentist. Despite the fact that molecular genetics studies allow to discriminate some dentine disorders, pathogenesis of radicular dentin dysplasia is still obscure. Type I dentin dysplasia is characterized by normal or slightly coloured crowns with no roots or only rudimentary roots, reduced pulp space in permanent teeth and incomplete or total obliteration of the pulp chambers, and periapical radiolucent areas or cysts which might result in premature loss of tooth. Fortunately, teeth demonstrate higher resistance to caries than normal teeth do.&#x0D; Dentin dysplasia type II is characterized by yellow, brown, grey, translucent primary teeth with complete pulpal obliteration. Permanent teeth are normal or might be slightly coloured. Roots are normal in size, but pulp chamber has pulp stones. A third type of dentine dysplasia or focal odontoblastic dysplasia has radiographic aspects of the other two types of disease.&#x0D; Also dentine dysplasia type I has subtypes Ia, Ib, Ic and Id. Dentine dysplasia Ia is characterized by complete obliteration of the pulp, disorder of root development, and many periapical radiolucent areas. A single small horizontally oriented and half-moon shaped pulp is presented in case of dentine dysplasia Ib, roots have a few millimetres length and frequent periapical radiolucencies. Dentine dysplasia Ic is characterized by the presence of two horizontal or vertical semicircle-shaped pulpal remnants which surround dentine in pulp chamber. Also teeth have shortened roots and variable periapical radiolucencies. Dentine dysplasia Id is characterized by the distinct pulp chambers with pulp stones in the coronal third of the root canal; periapical radiolucencies are possible as well. Aim of this study was to analyse clinical case of dentine dysplasia in 8,5-year-old boy.&#x0D; A 8,5-year old boy patient with parents came to a dental office due to caries cavity in tooth 62. Shape of tooth crowns was not changed and teeth with no signs of mobility; white lines and spots on teeth are were detected. Based on age, the decision of orthopantomogram was made to evaluate status of primary and permanent teeth. The image showed almost obliterated pulp chamber in both erupted and developing teeth and considerably shortened, blunted and malformed roots without a visible lumen of root canals in primary teeth. Periapical lesions were found about roots of primary molars and follicles of teeth 12 and 14 without caries lesions.&#x0D; Patient's medical history revealed no disturbance in general health. Clinical examination of the patient's mother did not show dental hard tissues disorders, but radiograph examination revealed such disorder in the orthopantomogram. Thus, history, clinical and radiographic findings revealed this case as dentine dysplasia type I subtype 1c inherited from mother.&#x0D; Oral rehabilitation of patients with dentine dysplasia type I require effective prevention and a complex approach. Thus, meticulous oral hygiene measures and dietary instructions, regular check-ups twice a year were established for this patient; orthodontic consultation was recommended. Varnish «Ftoplen-LC» was applied on the permanent teeth 3 times. To prevent early exfoliation, plan of preventive measures was developed included application of fluoride varnish twice a year and fissure sealing in the premolars in 9-10 years and in the second premolars in 12-13 years.&#x0D; Treatment of dentine dysplasia I type that depends on patient age and severity of disease may include also filling of carious teeth, orthodontic, surgical and orthodontic treatment. In this regard, dentist has to know developmental dental hard tissues disorders and select measures to prolong the retention of affected teeth maintaining them as long as possible.

Non-Syndromic Dentinogenesis Imperfecta Caused by Mild Mutations in COL1A2.

Hereditary dentin defects can be categorized as a syndromic form predominantly related to osteogenesis imperfecta (OI) or isolated forms without other non-oral phenotypes. Mutations in the gene encoding dentin sialophosphoprotein (DSPP) have been identified to cause dentinogenesis imperfecta (DGI) Types II and III and dentin dysplasia (DD) Type II. While DGI Type I is an OI-related syndromic phenotype caused mostly by monoallelic mutations in the genes encoding collagen type I alpha 1 chain (COL1A1) and collagen type I alpha 2 chain (COL1A2). In this study, we recruited families with non-syndromic dentin defects and performed candidate gene sequencing for DSPP exons and exon/intron boundaries. Three unrelated Korean families were further analyzed by whole-exome sequencing due to the lack of the DSPP mutation, and heterozygous COL1A2 mutations were identified: c.3233G>A, p.(Gly1078Asp) in Family 1 and c.1171G>A, p.(Gly391Ser) in Family 2 and 3. Haplotype analysis revealed different disease alleles in Families 2 and 3, suggesting a mutational hotspot. We suggest expanding the molecular genetic etiology to include COL1A2 for isolated dentin defects in addition to DSPP.

VPS4B deficiency causes early embryonic lethality and induces signal transduction disorders of cell endocytosis.

VPS4B (vacuolar protein sorting 4B), a member of the ATPase associated with diverse cellular activities (AAA) protein family, is a component of the endosomal sorting complexes required for transport machinery which regulates the internalization and lysosomal degradation of membrane proteins. We previously reported that VPS4B is one of the pathogenic genes related to dentin dysplasia type I, although its function was largely unknown. To investigate the role of VPS4B in tooth development, we deleted the Vps4b gene in mice. We found that heterozygous knockout mice (Vps4b+/- ) developed normally and were fertile. However, homozygous deletion of the Vps4b gene resulted in early embryonic lethality of Vps4b-/- mice at approximately embryonic day 9.5 (E9.5). To investigate the underlying molecular mechanisms, we examined the molecular functions of VPS4B in vivo and in vitro. Cell experiments showed that VPS4B influenced the proliferation, apoptosis, and cell cycle of transfected human neuroblastoma cells (IMR-32 cells) with over-expression or knockdown of VPS4B. Moreover, qRT-PCR detection showed that the mRNA expression levels of apoptosis-, cell cycle-, and endocytosis-related genes was significantly down or up-regulated in RNA interference-mediated knockdown of VPS4B in IMR-32 cells and Vps4b+/- E12.5 embryos. We accordingly speculated that signal transduction disorders of cell endocytosis are a contributing factor to the prenatal lethality of Vps4b-/- mice.

Guided endodontic treatment of multiple teeth with dentin dysplasia: a case report

BackgroundTo report the outcome of guided endodontic treatment (GET) of a case of dentin dysplasia with pulp canal calcification (PCC) and apical periodontitis based on the use of a 3D-printed template designed by merging cone-beam computed tomography (CBCT) and surface scan data.Case presentationA 12-year old female with radicular dentin dysplasia type I (DD-1) presented for endodontic treatment. Radiography revealed PCC in all teeth and apical radiolucency in seven teeth (12, 15, 26, 31, 32, 36 and 46). Tooth 36 had the most acute symptoms and was thus treated first by conventional access cavity preparation and root canal detection. Despite meticulous technique, the distal and mesiolingual canals were perforated. The perforations were immediately repaired with mineral trioxide aggregate, and the decision was made to switch to guided endodontic treatment for the remaining 6 teeth. CBCT and intraoral surface scans were acquired and matched using coDiagnostix planning software (Dental Wings Inc.), the respective drill positions for root canal location were determined, and templates were virtually designed and 3D-printed. The template was positioned on the respective tooth, and a customized drill was used to penetrate the calcified part of the root canal and perform minimally invasive access cavity preparation up to the apical region. All root canals were rapidly and successfully located with the templates. At 1-year follow-up, clear signs of apical healing were present in all treated teeth.ConclusionsIn patients with dentin dysplasia, conventional endodontic therapy is challenging. GET considerably facilitates the root canal treatment of teeth affected by dentin dysplasia.

Haploinsufficiency of Dspp Gene Causes Dentin Dysplasia Type II in Mice.

Dentin dysplasia (DD) and dentinogenesis imperfecta (DGI) patients have abnormal structure, morphology, and function of dentin. DD-II, DGI-II, and DGI-III are caused by heterozygous mutations in the dentin sialophosphoprotein (DSPP) gene in humans. Evidences have shown that loss of function of DSPP in Dspp knockout mice leads to phenotypes similar to DGI-III, and that the abnormal dentinogenesis is associated with decreased levels of DSPP, indicating that DSPP haploinsufficiency may play a role in dentinogenesis. Thus, to testify the haploinsufficiency of Dspp, we used a Dspp heterozygous mouse model to observe the phenotypes in the teeth and the surrounding tissues. We found that Dspp heterozygous mice displayed dentin phenotypes similar to DD-II at the ages of 12 and 18 months, which was characterized by excessive attrition of the enamel at the occlusal surfaces, thicker floor dentin of the pulp chamber, decreased pulp volume, and compromised mineralization of the dentin. In addition, the periodontium was also affected, exhibiting apical proliferation of the junctional epithelium, decreased height and width of the alveolar bone, and infiltration of the inflammatory cells, leading to the destruction of the periodontium. Both the dental and periodontal phenotypes were age-dependent, which were more severe at 18 months old than those at 12 months old. Our report is the first to claim the haploinsufficiency of Dspp gene and a DD-II mouse model, which can be further used to study the molecular mechanisms of DD-II.

VPS4B mutation impairs the osteogenic differentiation of dental follicle cells derived from a patient with dentin dysplasia type I

A splicing mutation in VPS4B can cause dentin dysplasia type I (DD-I), a hereditary autosomal-dominant disorder characterized by rootless teeth, the etiology of which is genetically heterogeneous. In our study, dental follicle cells (DFCs) were isolated and cultured from a patient with DD-I and compared with those from an age-matched, healthy control. In a previous study, this DD-I patient was confirmed to have a loss-of-function splicing mutation in VPS4B (IVS7 + 46C > G). The results from this study showed that the isolated DFCs were vimentin-positive and CK14-negative, indicating that the isolated cells were derived from the mesenchyme. DFCs harboring the VPS4B mutation had a significantly higher proliferation rate from day 3 to day 8 than control DFCs, indicating that VPS4B is involved in cell proliferation. The cells were then replenished with osteogenic medium to investigate how the VPS4B mutation affected osteogenic differentiation. Induction of osteogenesis, detected by alizarin red and alkaline phosphatase staining in vitro, was decreased in the DFCs from the DD-I patient compared to the control DFCs. Furthermore, we also found that the VPS4B mutation in the DD-I patient downregulated the expression of osteoblast-related genes, such as ALP, BSP, OCN, RUNX2, and their encoded proteins. These outcomes confirmed that the DD-I-associated VPS4B mutation could decrease the capacity of DFCs to differentiate during the mineralization process and may also impair physiological root formation and bone remodeling. This might provide valuable insights and implications for exploring the pathological mechanisms underlying DD-I root development.

Dentine Dysplasia Type II: Report of a Rare Case with Radiographic Criteria of Type I

Dentin dysplasia (DD) is a hereditary malformation of dental tissues affecting the dentin during the process of development. The teeth appear clinically normal; however, radigraphically the pulp morphology is abnormal and may be large or obliterated. The roots are diminutive, blunted, deformed or even absent. Periapical radiolucencies may be present without an apparent cause. The affected teeth may exhibit great mobility and exfoliate early even with minor trauma. In this article, we reported clinical and radiographic findings of a rare case of DD that have radiographic features of both DD- type II and DD type I in a 24 years old male patient visited the Out-Patient Dental Clinic of Qassim University, KSA.

MOLAR-INCISOR MALFORMATION: A NARRATIVE REVIEW

Introduction: “Molar-incisor malformation” (MIM) or “Molar root-incisor malformation” is a recently reported dental anomaly of unknown etiology, possibly associated with systemic complications, which affects the development of first permanent molar roots and dental enamel of central incisors. Objective: To conduct a literature review on “Molarincisor malformation”, also known as “Molar root-incisor malformation”, discussing its clinical, radiographic/tomographic and microscopic aspects; differential diagnosis and treatment possibilities. Sources of data: Electronic search was performed on the MEDLINE database in March 2021, without limit regarding the year of publication. The terms used were “molar-incisor malformation”, “molar-root incisor malformation”, “root malformation”, “root development”, “tooth roots”, “abnormalities”. Synthesis of data: Fifteen articles, most of them case series, were included. In general, medical historyrevealed clinical complications during pregnancy and / or the first years of life. Clinical features included tooth enamel defects in the cervical region of incisors and marked mobility of permanent molars and incisors. Radiographically, partially obliterated pulp chambers, short, thin and incomplete roots of first permanent molars and incisors, were observed. Microscopically, the occurrence of a hypercalcified dentin layer, in the form of a lens, inside the pulp chamber, at the level of the cementum-enamel junction, called“mineralized cervical diaphragm”, was reported. Conclusion: “Molar-incisor malformation” is an anomaly characterized by changes in root development, pulp chamber and enamel in permanent molars and incisors. The differential diagnosis includes Dentin Dysplasia type I and Regional Odontodysplasia. Medical and familyhistories are essential for the final diagnosis, and treatment, which despite not having an established protocol, requires a multidisciplinary approach and conventional treatments such as tooth extraction, endodontics, orthodontics, and dental implants.

Dentinal dysplasia type 1: A 3D micro-computed tomographic study of enamel, dentine and root canal morphology.

Dentine dysplasia type 1 is a rare and complex dental anomaly. Our aim was to conduct a morphometric assessment of a dentinal dysplasia type 1c (DD1c) caries-free mandibular second molar, extracted due to symptomatic apical periodontitis. Controls consisted of five intact mandibular second molars. Micro-computed tomography analysis showed that the DD1c volume % for enamel, dentine/cementum and pulp chamber fell in the 0.36th, 99.97th and 0.09th percentiles of the control teeth (P<0.01). It also revealed an extremely complicated root canal system in the DD1c tooth with a varying degree of dentine mineralisation and aberrant dentine deposition in the pulp chamber. A crack extending from the external tooth surface to the pulp chamber was identified as a potential site for microbial invasion. Clinical implications include preventive measures and early intervention in reversible pulpitis. Conclusion: Micro-CT imaging can be useful in establishing post-extraction diagnosis of cracks and phenomic characterisation of tooth anomalies.

Vacuolar protein sorting 4B regulates the proliferation and odontoblastic differentiation of human dental pulp stem cells through the Wnt-β-catenin signalling pathway

Our previous studies have revealed that a dominant mutation in vacuolar protein sorting 4B (VPS4B), a member of the AAA ATPase family, causes dentin dysplasia type I. The purpose of the present study was to investigate the roles of VPS4B in human dental pulp stem cells (hDPSCs) and to elucidate the underlying molecular mechanisms. In this study, we found that VPS4B was highly expressed in the dental pulp cells of the mouse molar tooth germ, and the expression of VPS4B increased significantly during the odontoblastic differentiation of hDPSCs. VPS4B downregulation inhibited the proliferation, migration, and odontoblastic differentiation of hDPSCs. Moreover, treatment with lithium chloride, an agonist of the Wnt-β-catenin signalling pathway, partially reversed the VPS4B knockdown-driven suppression of proliferation and of odontoblastic differentiation of hDPSCs. Collectively, our findings indicate that VPS4B, via Wnt-β-catenin signalling, acts as a regulator of the proliferation and differentiation of hDPSCs. Our results suggest potential therapeutic avenues for dentin formation and regenerative endodontics in patients with dentin dysplasia type I.