scholarly journals Functional Analysis of Ectodysplasin-A Mutations in X-Linked Non-Syndromic Hypodontia and Possible Involvement of X-Chromosome Inactivation

2021 ◽  
Author(s):  
Yuhua Pan ◽  
Ting Lu ◽  
Ling Peng ◽  
Qi Zeng ◽  
Xiangyu Huang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Functional Analysis ◽  
X Chromosome ◽  
Dental Pulp ◽  
X Chromosome Inactivation ◽  
Dental Pulp Stem Cells ◽  
Chromosome Inactivation ◽  
Tooth Agenesis ◽  
Human Dental Pulp ◽  
The Impact

Abstract BackgroundMutations of the Ectodysplasin-A (EDA) gene are generally associated with other developmental anomalies (syndrome hypohidrotic ectodermal dysplasia) or as an isolated condition (non-syndromic tooth agenesis). The influence of EDA mutations on dentinogenesis and odontoblast differentiation have not been reported. The aim of the present study was to identify genetic clues for familial nonsyndromic oligodontia and explore the underlying mechanisms, focusing on the role of human dental pulp stem cells (hDPSCs).MethodsThe candidate genes sequences were performed by PCR amplification and Sanger sequencing. Functional analysis and pathogenesis associated with EDA mutations in hDPSCs were also investigated to explore the impact of the identified mutation on this phenotype. Capillary electrophoresis (CE) was used to detect X chromosome inactivation (XCI) on the blood of female carrier.ResultsIn this study, we identified a reported EDA mutation in a Chinese family：a missense mutation c.1013C>T (Thr338Met). Transfection of hDPSCs with mutant EDA lentivirus decreased the expression of EDA and dentin sialophosphoprotein (DSPP) compared with those transfected with control EDA lentivirus. Mechanically, the mutant EDA inhibited the activation of the NF-κB pathway. The results of CE showed that symptomatic female carrier had a skewed XCI with a preferential inactivation of the X chromosome carrying the normal allele.ConclusionIn summary, we demonstrated EDA mutation result in non-syndromic tooth agenesis in heterozygous females and mechanically EDA regulates odontogenesis through the NF-κB signaling pathway in human dental pulp stem cells.

Functional analysis of ectodysplasin-A mutations and involvement of X-chromosome inactivation

2021 ◽  
Author(s):  
Yuhua Pan ◽  
Ting Lu ◽  
Ling Peng ◽  
Qi Zeng ◽  
Xiangyu Huang ◽  
...  
Keyword(s):  
Functional Analysis ◽  
X Chromosome ◽  
Pcr Amplification ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Tooth Agenesis ◽  
Human Dental Pulp ◽  
Underlying Mechanisms ◽  
The Impact ◽  
Female Carriers

Abstract Objectives: The aim of this study was to identify genetic clues for the causes of familial non-syndromic oligodontia and explore the underlying mechanisms involved, while focusing on the role of human dental pulp stem cells (hDPSCs).Materials and Methods: Candidate gene sequences were obtained by PCR amplification and Sanger sequencing. Functional analysis was conducted, and the pathogenesis associated with EDA mutations in hDPSCs was investigated to explore the impact of the identified mutation on the phenotype. Capillary electrophoresis (CE) was used to detect X chromosome inactivation (XCI) in the blood of female carriers.Results: In this study, we identified an EDA mutation in a Chinese family：the missense mutation c.1013C>T (Thr338Met). Transfection of hDPSCs with a mutant EDA lentivirus decreased the expression of EDA and dentin sialophosphoprotein (DSPP) compared with transfection of control EDA lentivirus. Mechanistically, mutant EDA inhibited the activation of the NF-κB pathway. The CE results showed that symptomatic female carriers had a skewed XCI with a preferential inactivation of the X chromosome that carried the normal allele.Conclusions: In summary, we demonstrated that EDA mutations result in non-syndromic tooth agenesis in heterozygous females and that, mechanistically, EDA regulates odontogenesis through the NF-κB signalling pathway in hDPSCs.Clinical Relevance: Due to the large heterogeneity of tooth agenesis, this study provided a genetic basis for individuals who exhibit similar clinical phenotypes.

scholarly journals Functional analysis of Ectodysplasin-A mutations in X-linked non-syndromic hypodontia and possible involvement of X-chromosome inactivation

2021 ◽  
Author(s):  
Yuhua Pan ◽  
Ting Lu ◽  
Ling Peng ◽  
Qi Zeng ◽  
Xiangyu Huang ◽  
...  
Keyword(s):  
Functional Analysis ◽  
X Chromosome ◽  
Pcr Amplification ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Tooth Agenesis ◽  
Human Dental Pulp ◽  
Underlying Mechanisms ◽  
The Impact ◽  
Female Carriers

Abstract Background: Mutations of the Ectodysplasin-A (EDA) gene are generally associated with syndrome hypohidrotic ectodermal dysplasia or non-syndromic tooth agenesis. The influence of EDA mutations on dentinogenesis and odontoblast differentiation have not been reported. The aim of this study was to identify genetic clues for the causes of familial non-syndromic oligodontia and explore the underlying mechanisms involved, while focusing on the role of human dental pulp stem cells (hDPSCs). Materials and Methods: Candidate gene sequences were obtained by PCR amplification and Sanger sequencing. Functional analysis was conducted, and the pathogenesis associated with EDA mutations in hDPSCs was investigated to explore the impact of the identified mutation on the phenotype. Capillary electrophoresis (CE) was used to detect X chromosome inactivation (XCI) in the blood of female carriers. Results: In this study, we identified an EDA mutation in a Chinese family：the missense mutation c.1013C>T (Thr338Met). Transfection of hDPSCs with a mutant EDA lentivirus decreased the expression of EDA and dentin sialophosphoprotein (DSPP) compared with transfection of control EDA lentivirus. Mechanistically, mutant EDA inhibited the activation of the NF-κB pathway. The CE results showed that symptomatic female carriers had a skewed XCI with a preferential inactivation of the X chromosome that carried the normal allele. Conclusions: In summary, we demonstrated that EDA mutations result in non-syndromic tooth agenesis in heterozygous females and that, mechanistically, EDA regulates odontogenesis through the NF-κB signalling pathway in hDPSCs. Due to the large heterogeneity of tooth agenesis, this study provided a genetic basis for individuals who exhibit similar clinical phenotypes.

scholarly journals Functional Analysis of Ectodysplasin-A Mutations in X-Linked Nonsyndromic Hypodontia and Possible Involvement of X-Chromosome Inactivation

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yuhua Pan ◽  
Ting Lu ◽  
Ling Peng ◽  
Qi Zeng ◽  
Xiangyu Huang ◽  
...  
Keyword(s):  
Functional Analysis ◽  
X Chromosome ◽  
Pcr Amplification ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Chinese Family ◽  
Tooth Agenesis ◽  
Underlying Mechanisms ◽  
The Impact ◽  
Female Carriers

Background. Mutations of the Ectodysplasin-A (EDA) gene are generally associated with syndrome hypohidrotic ectodermal dysplasia or nonsyndromic tooth agenesis. The influence of EDA mutations on dentinogenesis and odontoblast differentiation has not been reported. The aim of this study was to identify genetic clues for the causes of familial nonsyndromic oligodontia and explore the underlying mechanisms involved, while focusing on the role of human dental pulp stem cells (hDPSCs). Materials and Methods. Candidate gene sequences were obtained by PCR amplification and Sanger sequencing. Functional analysis was conducted, and the pathogenesis associated with EDA mutations in hDPSCs was investigated to explore the impact of the identified mutation on the phenotype. Capillary electrophoresis (CE) was used to detect X-chromosome inactivation (XCI) in the blood of female carriers. Results. In this study, we identified an EDA mutation in a Chinese family: the missense mutation c.1013C>T (Thr338Met). Transfection of hDPSCs with a mutant EDA lentivirus decreased the expression of EDA and dentin sialophosphoprotein (DSPP) compared with transfection of control EDA lentivirus. Mechanistically, mutant EDA inhibited the activation of the NF-κB pathway. The CE results showed that symptomatic female carriers had a skewed XCI with a preferential inactivation of the X chromosome that carried the normal allele. Conclusions. In summary, we demonstrated that EDA mutations result in nonsyndromic tooth agenesis in heterozygous females and that, mechanistically, EDA regulates odontogenesis through the NF-κB signalling pathway in hDPSCs. Due to the large heterogeneity of tooth agenesis, this study provided a genetic basis for individuals who exhibit similar clinical phenotypes.

Chrysin induces osteogenic differentiation of human dental pulp stem cells

2021 ◽  
Vol 400 (2) ◽  
pp. 112466
Author(s):  
J.F. Huo ◽  
M.L. Zhang ◽  
X.X. Wang ◽  
D.H. Zou
Keyword(s):  
Stem Cells ◽  
Osteogenic Differentiation ◽  
Dental Pulp ◽  
Dental Pulp Stem Cells ◽  
Human Dental Pulp

scholarly journals Methylglyoxal-Dependent Glycative Stress Is Prevented by the Natural Antioxidant Oleuropein in Human Dental Pulp Stem Cells through Nrf2/Glo1 Pathway

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 716
Author(s):  
Simona Delle Delle Monache ◽  
Fanny Pulcini ◽  
Roberta Frosini ◽  
Vincenzo Mattei ◽  
Vincenzo Nicola Talesa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dental Pulp ◽  
Dental Pulp Stem Cells ◽  
Great Promise ◽  
Oral Diseases ◽  
Bioactive Component ◽  
Glycation End Products ◽  
Abnormal Accumulation ◽  
Synthetic Agents ◽  
Human Dental Pulp

Methylglyoxal (MG) is a potent precursor of glycative stress (abnormal accumulation of advanced glycation end products, AGEs), a relevant condition underpinning the etiology of several diseases, including those of the oral cave. At present, synthetic agents able to trap MG are known; however, they have never been approved for clinical use because of their severe side effects. Hence, the search of bioactive natural scavengers remains a sector of strong research interest. Here, we investigated whether and how oleuropein (OP), the major bioactive component of olive leaf, was able to prevent MG-dependent glycative stress in human dental pulp stem cells (DPSCs). The cells were exposed to OP at 50 µM for 24 h prior to the administration of MG at 300 µM for additional 24 h. We found that OP prevented MG-induced glycative stress and DPSCs impairment by restoring the activity of Glyoxalase 1 (Glo1), the major detoxifying enzyme of MG, in a mechanism involving the redox-sensitive transcription factor Nrf2. Our results suggest that OP holds great promise for the development of preventive strategies for MG-derived AGEs-associated oral diseases and open new paths in research concerning additional studies on the protective potential of this secoiridoid.

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