The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs(lncRNAs).However,the dynamics of lncRNA expression during human tooth development remain poorly understoo...The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs(lncRNAs).However,the dynamics of lncRNA expression during human tooth development remain poorly understood.In this research,we examined the lncRNAs present in the dental epithelium(DE)and dental mesenchyme(DM)at the late bud,cap,and early bell stages of human fetal tooth development through bulk RNA sequencing.Developmental regulators co-expressed with neighboring lncRNAs were significantly enriched in odontogenesis.Specific lncRNAs expressed in the DE and DM,such as PANCR,MIR205HG,DLX6-AS1,and DNM3OS,were identified through a combination of bulk RNA sequencing and single-cell analysis.Further subcluster analysis revealed lncRNAs specifically expressed in important regions of the tooth germ,such as the inner enamel epithelium and coronal dental papilla(CDP).Functionally,we demonstrated that CDP-specific DLX6-AS1 enhanced odontoblastic differentiation in human tooth germ mesenchymal cells and dental pulp stem cells.These findings suggest that lncRNAs could serve as valuable cell markers for tooth development and potential therapeutic targets for tooth regeneration.展开更多
Tissue interactions play a crucial role in tooth development.Notably,extracellular vesicle-mediated interactions between the mandible and tooth germ are considered essential.Here,we revealed that mandible extracellula...Tissue interactions play a crucial role in tooth development.Notably,extracellular vesicle-mediated interactions between the mandible and tooth germ are considered essential.Here,we revealed that mandible extracellular vesicles could modulate the proliferation and differentiation of dental mesenchymal cells by regulating the histone demethylase KDM2B.Further investigation showed that mandible derived extracellular vesicles could deliver miR-206 to KDM2B,thereby regulating tooth development.An animal study demonstrated that the miR-206/KDM2B pathway affected tooth morphogenesis and mineralization after eight weeks of subcutaneous transplantation in nude mice.In conclusion,this study suggested that the mandible played a critical role in tooth morphogenesis and mineralization,which could be a potential therapeutic target for abnormal tooth development and an alternative model for tooth regeneration.展开更多
several heat shock proteins have been investigated in relation to tooth development, no available information is available about the spatial and temporal expression pattern of heat shock protein 60 （Hsp 60）. To char...several heat shock proteins have been investigated in relation to tooth development, no available information is available about the spatial and temporal expression pattern of heat shock protein 60 （Hsp 60）. To characterize Hsp 60 expression in the structures of the developing tooth germ, we used Western blotting, immunohistochemistry and in situ hybridization. Hsp 60 was present in high amounts in the inner and outer enamel epithelia, enamel knot （EK） and stratum intermedium （SI）. Hsp 60 also appeared in odontoblasts beginning in the bell stage. To obtain data on the possible effect of Hsp 60 on isolated lower incisors from mice, we performed in vitro culturing. To investigate the effect of exogenous Hsp 60 on the cell cycle during culturing, we used the 5-bromo-2- deoxyuridine （BrdU） incorporation test on dental cells. Exogenously administered Hsp 60 caused bluntness at the apical part of the 16.5-day-old tooth germs, but it did not influence the proliferation rate of dental cells. We identified the expression of Hsp 60 in the developing tooth germ, which was present in high concentrations in the inner and outer enamel epithelia, EK, SI and odontoblasts. High concentration of exogenous Hsp 60 can cause abnormal morphology of the tooth germ, but it did not influence the proliferation rate of the dental cells. Our results suggest that increased levels of Hsp 60 may cause abnormalities in the morphological development of the tooth germ and support the data on the significance of Hsp during the developmental processes.展开更多
Histone methylation is one of the most widely studied post-transcriptional modifications. It is thought to be an important epigenetic event that is closely associated with cell fate determination and differentiation. ...Histone methylation is one of the most widely studied post-transcriptional modifications. It is thought to be an important epigenetic event that is closely associated with cell fate determination and differentiation. To explore the spatiotemporal expression of histone H3 lysine 4trimethylation（H3K4me3） and histone H3 lysine 27 trimethylation（H3K27me3） epigenetic marks and methylation or demethylation transferases in tooth organ development, we measured the expression of SET7, EZH2, KDM5 B and JMJD3 via immunohistochemistry and quantitative polymerase chain reaction（qP CR） analysis in the first molar of BALB/c mice embryos at E13.5, E15.5, E17.5, P0 and P3, respectively. We also measured the expression of H3K4me3 and H3K27me3 with immunofluorescence staining. During murine tooth germ development, methylation or demethylation transferases were expressed in a spatial–temporal manner. The bivalent modification characterized by H3K4me3 and H3K27me3 can be found during the tooth germ development, as shown by immunofluorescence. The expression of SET7, EZH2 as methylation transferases and KDM5 B and JMJD3 as demethylation transferases indicated accordingly with the expression of H3K4me3 and H3K27me3 respectively to some extent. The bivalent histone may play a critical role in tooth organ development via the regulation of cell differentiation.展开更多
BACKGROUND Accumulating evidence suggests that the maxillary process,to which cranial crest cells migrate,is essential to tooth development.Emerging studies indicate that Cd271 plays an essential role in odontogenesis...BACKGROUND Accumulating evidence suggests that the maxillary process,to which cranial crest cells migrate,is essential to tooth development.Emerging studies indicate that Cd271 plays an essential role in odontogenesis.However,the underlying mechanisms have yet to be elucidated.AIM To establish the functionally heterogeneous population in the maxillary process,elucidate the effects of Cd271 deficiency on gene expression differences.METHODS p75NTR knockout(Cd271-/-)mice(from American Jackson laboratory)were used to collect the maxillofacial process tissue of p75NTR knockout mice,and the wildtype maxillofacial process of the same pregnant mouse wild was used as control.After single cell suspension,the cDNA was prepared by loading the single cell suspension into the 10x Genomics Chromium system to be sequenced by NovaSeq6000 sequencing system.Finally,the sequencing data in Fastq format were obtained.The FastQC software is used to evaluate the quality of data and CellRanger analyzed the data.The gene expression matrix is read by R software,and Seurat is used to control and standardize the data,reduce the dimension and cluster.We search for marker genes for subgroup annotation by consulting literature and database;explore the effect of p75NTR knockout on mesenchymal stem cells(MSCs)gene expression and cell proportion by cell subgrouping,differential gene analysis,enrichment analysis and protein-protein interaction network analysis;understand the interaction between MSCs cells and the differentiation trajectory and gene change characteristics of p75NTR knockout MSCs by cell communication analysis and pseudo-time analysis.Last we verified the findings single cell sequencing in vitro.RESULTS We identified 21 cell clusters,and we re-clustered these into three subclusters.Importantly,we revealed the cell–cell communication networks between clusters.We clarified that Cd271 was significantly associated with the regulation of mineralization.CONCLUSION This study provides comprehensive mechanistic insights into the maxillary-process-derived MSCs and demonstrates that Cd271 is significantly associated with the odontogenesis in mesenchymal populations.展开更多
This report,"Mandible exosomal ssc-mir-133b regulates tooth development in miniature swine via endogenous apoptosis" by Li et al. is an important step forward in describing the factors that control tooth dev...This report,"Mandible exosomal ssc-mir-133b regulates tooth development in miniature swine via endogenous apoptosis" by Li et al. is an important step forward in describing the factors that control tooth development in a large animal model. That many of the regulatory miRNA pathways have been elucidated in murine species have always begged the question as to how relevant they展开更多
The root is crucial for the physiological function of the tooth, and a healthy root allows an artificial crown to function as required clinically. Tooth crown development has been studied intensively during the last f...The root is crucial for the physiological function of the tooth, and a healthy root allows an artificial crown to function as required clinically. Tooth crown development has been studied intensively during the last few decades, but root development remains not well understood. Here we review the root development processes, including cell fate determination, induction of odontoblast and cementoblast differentiation, interaction of root epithelium and mesenchyme, and other molecular mechanisms. This review summarizes our current understanding of the signaling cascades and mechanisms involved in root development. It also sets the stage for de novo tooth regeneration.展开更多
The pharyngeal dental formula of Mylopharyngodon piceus is 4-5 as a rule, and the dentition isasymmetrical. It is difficult to identify each tooth in the larval dentition. In this paper the appearancepattem of tooth g...The pharyngeal dental formula of Mylopharyngodon piceus is 4-5 as a rule, and the dentition isasymmetrical. It is difficult to identify each tooth in the larval dentition. In this paper the appearancepattem of tooth germ with developmental process in this fish is described in detail. The formationpattern of the left dentition is contrasted with that of the right one. In the developmental process,the left pharyngeal dentition lacks teeth at position An3. Thus the left dentition is D-type as designatedby Nakajima(1984), while the right one is A-type.展开更多
Dental mesenchymal stem cells(DMSCs)are pivotal for tooth development and periodontal tissue health and play an important role in tissue engineering and regenerative medicine because of their multidirectional differen...Dental mesenchymal stem cells(DMSCs)are pivotal for tooth development and periodontal tissue health and play an important role in tissue engineering and regenerative medicine because of their multidirectional differentiation potential and self-renewal ability.The cellular microenvironment regulates the fate of stem cells and can be modified using various optimization techniques.These methods can influence the cellular microenvironment,activate disparate signaling pathways,and induce different biological effects.“Epigenetic regulation”refers to the process of influencing gene expression and regulating cell fate without altering DNA sequences,such as histone methylation.Histone methylation modifications regulate pivotal transcription factors governing DMSCs differentiation into osteo-/odontogenic lineages.The most important sites of histone methylation in tooth organization were found to be H3K4,H3K9,and H3K27.Histone methylation affects gene expression and regulates stem cell differentiation by maintaining a delicate balance between major trimethylation sites,generating distinct chromatin structures associated with specific downstream transcriptional states.Several crucial signaling pathways associated with osteogenic differentiation are susceptible to modulation via histone methylation modifications.A deeper understanding of the regulatory mechanisms governing histone methylation modifications in osteo-/odontogenic differentiation and immune-inflammatory responses of DMSCs will facilitate further investigation of the epigenetic regulation of histone methylation in DMSC-mediated tissue regeneration and inflammation.Here is a concise overview of the pivotal functions of epigenetic histone methylation at H3K4,H3K9,and H3K27 in the regulation of osteo-/odontogenic differentiation and renewal of DMSCs in both non-inflammatory and inflammatory microenvironments.This review summarizes the current research on these processes in the context of tissue regeneration and therapeutic interventions.展开更多
Mammalian tooth development is largely dependent on sequential and reciprocal epithelial-mesenchymal interactions.These processes involve a series of inductive and permissive interactions that result in the determinat...Mammalian tooth development is largely dependent on sequential and reciprocal epithelial-mesenchymal interactions.These processes involve a series of inductive and permissive interactions that result in the determination,differentiation,and organization of odontogenic tissues.Multiple signaling molecules,including BMPs,FGFs,Shh,and Wnt proteins,have been implicated in mediating these tissue interactions.Transcription factors participate in epithelial-mesenchymal interactions via linking the signaling loops between tissue layers by responding to inductive signals and regulating the expression of other signaling molecules.Adult stem cells are highly plastic and multipotent.These cells including dental pulp stem cells and bone marrow stromal cells could be reprogrammed into odontogenic fate and participated in tooth formation.Recent progress in the studies of molecular basis of tooth development,adult stem cell biology,and regene-ration will provide fundamental knowledge for the realization of human tooth regeneration in the near future.展开更多
The tooth root cementum is a thin, mineralized tissue covering the root dentin that is present primarily as acellular cementum on the cervical root and cellular cementum covering the apical root. While cementum shares...The tooth root cementum is a thin, mineralized tissue covering the root dentin that is present primarily as acellular cementum on the cervical root and cellular cementum covering the apical root. While cementum shares many properties in common with bone and dentin, it is a unique mineralized tissue and acellular cementum is critical for attachment of the tooth to the surrounding periodontal ligament （PDL）. Resources for methodologies for hard tissues often overlook cementum and approaches that may be of value for studying this tissue. To address this issue, this report offers detailed methodology, as well as comparisons of several histological and immunohistochemical stains available for imaging the cementum-PDL complex by light microscopy. Notably, the infrequently used Alcian blue stain with nuclear fast red counterstain provided utility in imaging cementum in mouse, porcine and human teeth. While no truly unique extracellular matrix markers have been identified to differentiate cementum from the other hard tissues, immunohistochemistry for detection of bone sialoprotein （BSP）, osteopontin （OPN）, and dentin matrix protein 1 （DMP1） is a reliable approach for studying both acellular and cellular cementum and providing insight into developmental biology of these tissues. Histoloeical and immunohistochemical aooroaches Drovide insight on developmental biology of cementum.展开更多
Tooth development relies on sequential and reciprocal interactions between the epithelial and mesenchymal tissues, and it is continuously regulated by a variety of conserved and specific temporal-spatial signalling pa...Tooth development relies on sequential and reciprocal interactions between the epithelial and mesenchymal tissues, and it is continuously regulated by a variety of conserved and specific temporal-spatial signalling pathways. It is well known that suspensions of tooth germ cells can form tooth-like structures after losing the positional information provided by the epithelial and mesenchymal tissues. However, the particular stage in which the tooth germ cells start to form tooth-like structures after losing their positional information remains unclear. In this study, we investigated the reassociation of tooth germ cells suspension from different morphological stages during tooth development and the phosphorylation of Smad2/3 in this process. Four tooth morphological stages were designed in this study. The results showed that tooth germ cells formed odontogenic tissue at embryonic day （E） 14.5, which is referred to as the cap stage, and they formed tooth-like structures at E16.5, which is referred to as the early bell stage, and E18.5, which is referred to as the late bell stage. Moreover, the transforming growth factor-β signalling pathway might play a role in this process.展开更多
Tooth crown morphogenesis is tightly regulated by the proliferation and differentiation of dental epithelial cells.Globoside(Gb4),a globo-series glycosphingolipid,is highly expressed during embryogenesis as well as or...Tooth crown morphogenesis is tightly regulated by the proliferation and differentiation of dental epithelial cells.Globoside(Gb4),a globo-series glycosphingolipid,is highly expressed during embryogenesis as well as organogenesis,including tooth development.We previously reported that Gb4 is dominantly expressed in the neutral lipid fraction of dental epithelial cells.However,because its functional role in tooth development remains unknown,we investigated the involvement of Gb4 in dental epithelial cell differentiation.The expression of Gb4 was detected in ameloblasts of postnatal mouse molars and incisors.A cell culture analysis using HAT-7 cells,a rat-derived dental epithelial cell line,revealed that Gb4 did not promote dental epithelial cell proliferation.Interestingly,exogenous administration of Gb4 enhanced the gene expression of enamel extracellular matrix proteins such as ameloblastin,amelogenin,and enamelin in dental epithelial cells as well as in developing tooth germs.Gb4 also induced the expression of TrkB,one of the key receptors required for ameloblast induction in dental epithelial cells.In contrast,Gb4 downregulated the expression of p75,a receptor for neurotrophins(including neurotrophin-4)and a marker of undifferentiated dental epithelial cells.In addition,we found that exogenous administration of Gb4 to dental epithelial cells stimulated the extracellular signal-regulated kinase and p38 mitogen-activated protein kinase signalling pathways.Furthermore,Gb4 induced the expression of epiprofin and Runx2,the positive regulators for ameloblastin gene transcription.Thus,our results suggest that Gb4 contributes to promoting the differentiation of dental epithelial cells into ameloblasts.展开更多
Tooth tissue engineering is an emerging biotechnique that will provide replacemental teeth for patients suffering from different diseases causing tooth loss. Although some attempts have been tried to generate whole to...Tooth tissue engineering is an emerging biotechnique that will provide replacemental teeth for patients suffering from different diseases causing tooth loss. Although some attempts have been tried to generate whole tooth both in vivo and in vitro, the lack of the knowledge for tooth initiation and development, as well as for tooth shape controlling mechanisms greatly impede the progress of this technique. This article reviewed and discussed some recent findings in tooth tissue engineering related to the cell resource, the concept of reconstruction and regeneration, the application of artificial scaffolds, together with the methods of organ culture and implantation.展开更多
Aim To characterize the odontogenic capability of apical bud and phenotypical change of apical bud cells （ABCs） in different microenvironment.Methodology Incisor apical bud tissues from neonatal SD rat were dissecte...Aim To characterize the odontogenic capability of apical bud and phenotypical change of apical bud cells （ABCs） in different microenvironment.Methodology Incisor apical bud tissues from neonatal SD rat were dissected and transplanted into the renal capsules to determine their odontogenic capability. Meanwhile ABCs were cultured and purified by repeated differential trypsinization. Then ABCs were cultured with conditioned medium from developing apical complex cells （DAC-CM）. Immunocytochemistry, reverse transcriptase polymerase chain reaction （RT-PCR） and scanning electron microscope （SEM） were performed to compare the biolo- gical change of ABC treated with or without DAC-CM. Results First we confirmed the ability of apical bud to form crown-like structure ectopically. Equally important, by using the developing apical complex （DAC） condi- tioned medium, we found the microenvironment created by root could abrogate the ＂crown＂ features of ABCs and promote their proliferation and differentiation. Conclusion ABCs possess odontogenic capability to form crown-like tissues and this property can be affected by root-produced microenvironment.展开更多
基金supported by the National Key Research and Development Program(2022YFA1104401)Beijing Municipal Government grant(Beijing Laboratory of Oral Health,PXM2021-014226-000041)+3 种基金Beijing Municipal Govemment(Beijing Scholar Program,PXM2021-014226-000020)National Natural Science Foundation of China(82030031,92149301,81991504,L2224038,82270945)Innovation Research Team Project of Beijing Stomatological Hospital,Capital Medical University(CXTD202201)Chinese Research Unit of Tooth Development and Regeneration,Academy of Medical Sciences(2019-12M-5-031).
文摘The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs(lncRNAs).However,the dynamics of lncRNA expression during human tooth development remain poorly understood.In this research,we examined the lncRNAs present in the dental epithelium(DE)and dental mesenchyme(DM)at the late bud,cap,and early bell stages of human fetal tooth development through bulk RNA sequencing.Developmental regulators co-expressed with neighboring lncRNAs were significantly enriched in odontogenesis.Specific lncRNAs expressed in the DE and DM,such as PANCR,MIR205HG,DLX6-AS1,and DNM3OS,were identified through a combination of bulk RNA sequencing and single-cell analysis.Further subcluster analysis revealed lncRNAs specifically expressed in important regions of the tooth germ,such as the inner enamel epithelium and coronal dental papilla(CDP).Functionally,we demonstrated that CDP-specific DLX6-AS1 enhanced odontoblastic differentiation in human tooth germ mesenchymal cells and dental pulp stem cells.These findings suggest that lncRNAs could serve as valuable cell markers for tooth development and potential therapeutic targets for tooth regeneration.
基金supported by the National Natural Science Foundation of China(No.82071078,82370939)the Shaanxi Provincial High-level Talent Program and Young Talent Support Plan of Xi’an Jiaotong University.
文摘Tissue interactions play a crucial role in tooth development.Notably,extracellular vesicle-mediated interactions between the mandible and tooth germ are considered essential.Here,we revealed that mandible extracellular vesicles could modulate the proliferation and differentiation of dental mesenchymal cells by regulating the histone demethylase KDM2B.Further investigation showed that mandible derived extracellular vesicles could deliver miR-206 to KDM2B,thereby regulating tooth development.An animal study demonstrated that the miR-206/KDM2B pathway affected tooth morphogenesis and mineralization after eight weeks of subcutaneous transplantation in nude mice.In conclusion,this study suggested that the mandible played a critical role in tooth morphogenesis and mineralization,which could be a potential therapeutic target for abnormal tooth development and an alternative model for tooth regeneration.
基金supported by the European Union and the State of Hungary and co-financed by the European Social Fund in the framework of TA′MOP 4.2.4.A/2-11-12012-0001‘National Excellence Program’supported by a Ja′nos Bolyai fellowship from the Hungarian Academy of Science
文摘several heat shock proteins have been investigated in relation to tooth development, no available information is available about the spatial and temporal expression pattern of heat shock protein 60 （Hsp 60）. To characterize Hsp 60 expression in the structures of the developing tooth germ, we used Western blotting, immunohistochemistry and in situ hybridization. Hsp 60 was present in high amounts in the inner and outer enamel epithelia, enamel knot （EK） and stratum intermedium （SI）. Hsp 60 also appeared in odontoblasts beginning in the bell stage. To obtain data on the possible effect of Hsp 60 on isolated lower incisors from mice, we performed in vitro culturing. To investigate the effect of exogenous Hsp 60 on the cell cycle during culturing, we used the 5-bromo-2- deoxyuridine （BrdU） incorporation test on dental cells. Exogenously administered Hsp 60 caused bluntness at the apical part of the 16.5-day-old tooth germs, but it did not influence the proliferation rate of dental cells. We identified the expression of Hsp 60 in the developing tooth germ, which was present in high concentrations in the inner and outer enamel epithelia, EK, SI and odontoblasts. High concentration of exogenous Hsp 60 can cause abnormal morphology of the tooth germ, but it did not influence the proliferation rate of the dental cells. Our results suggest that increased levels of Hsp 60 may cause abnormalities in the morphological development of the tooth germ and support the data on the significance of Hsp during the developmental processes.
基金supported by National Science Foundation of China (Grant No. 81371136) to Xue-Dong ZhouNational Science Foundation of China (Grant No. 81200760 and 81470711) to Li-Wei Zheng
文摘Histone methylation is one of the most widely studied post-transcriptional modifications. It is thought to be an important epigenetic event that is closely associated with cell fate determination and differentiation. To explore the spatiotemporal expression of histone H3 lysine 4trimethylation（H3K4me3） and histone H3 lysine 27 trimethylation（H3K27me3） epigenetic marks and methylation or demethylation transferases in tooth organ development, we measured the expression of SET7, EZH2, KDM5 B and JMJD3 via immunohistochemistry and quantitative polymerase chain reaction（qP CR） analysis in the first molar of BALB/c mice embryos at E13.5, E15.5, E17.5, P0 and P3, respectively. We also measured the expression of H3K4me3 and H3K27me3 with immunofluorescence staining. During murine tooth germ development, methylation or demethylation transferases were expressed in a spatial–temporal manner. The bivalent modification characterized by H3K4me3 and H3K27me3 can be found during the tooth germ development, as shown by immunofluorescence. The expression of SET7, EZH2 as methylation transferases and KDM5 B and JMJD3 as demethylation transferases indicated accordingly with the expression of H3K4me3 and H3K27me3 respectively to some extent. The bivalent histone may play a critical role in tooth organ development via the regulation of cell differentiation.
基金National Natural Science Foundation of China(General Program),No.31870971Medical Health Science and Technology Project of Zhejiang Province,No.2023KY155.
文摘BACKGROUND Accumulating evidence suggests that the maxillary process,to which cranial crest cells migrate,is essential to tooth development.Emerging studies indicate that Cd271 plays an essential role in odontogenesis.However,the underlying mechanisms have yet to be elucidated.AIM To establish the functionally heterogeneous population in the maxillary process,elucidate the effects of Cd271 deficiency on gene expression differences.METHODS p75NTR knockout(Cd271-/-)mice(from American Jackson laboratory)were used to collect the maxillofacial process tissue of p75NTR knockout mice,and the wildtype maxillofacial process of the same pregnant mouse wild was used as control.After single cell suspension,the cDNA was prepared by loading the single cell suspension into the 10x Genomics Chromium system to be sequenced by NovaSeq6000 sequencing system.Finally,the sequencing data in Fastq format were obtained.The FastQC software is used to evaluate the quality of data and CellRanger analyzed the data.The gene expression matrix is read by R software,and Seurat is used to control and standardize the data,reduce the dimension and cluster.We search for marker genes for subgroup annotation by consulting literature and database;explore the effect of p75NTR knockout on mesenchymal stem cells(MSCs)gene expression and cell proportion by cell subgrouping,differential gene analysis,enrichment analysis and protein-protein interaction network analysis;understand the interaction between MSCs cells and the differentiation trajectory and gene change characteristics of p75NTR knockout MSCs by cell communication analysis and pseudo-time analysis.Last we verified the findings single cell sequencing in vitro.RESULTS We identified 21 cell clusters,and we re-clustered these into three subclusters.Importantly,we revealed the cell–cell communication networks between clusters.We clarified that Cd271 was significantly associated with the regulation of mineralization.CONCLUSION This study provides comprehensive mechanistic insights into the maxillary-process-derived MSCs and demonstrates that Cd271 is significantly associated with the odontogenesis in mesenchymal populations.
文摘This report,"Mandible exosomal ssc-mir-133b regulates tooth development in miniature swine via endogenous apoptosis" by Li et al. is an important step forward in describing the factors that control tooth development in a large animal model. That many of the regulatory miRNA pathways have been elucidated in murine species have always begged the question as to how relevant they
基金supported by grants from the NIDCR, NIH (DE012711 and DE014078) to Yang ChaiNational Natural Science Foundation of China (81170943)+1 种基金Beijing Natural Science Foundation (7122051)Funding for Talents in Beijing (D) (2010D003034000012) to Xiao-Feng Huang
文摘The root is crucial for the physiological function of the tooth, and a healthy root allows an artificial crown to function as required clinically. Tooth crown development has been studied intensively during the last few decades, but root development remains not well understood. Here we review the root development processes, including cell fate determination, induction of odontoblast and cementoblast differentiation, interaction of root epithelium and mesenchyme, and other molecular mechanisms. This review summarizes our current understanding of the signaling cascades and mechanisms involved in root development. It also sets the stage for de novo tooth regeneration.
基金This project was funded by the International Cooperation of japan-Chinathe National Natural Science Foundation of China
文摘The pharyngeal dental formula of Mylopharyngodon piceus is 4-5 as a rule, and the dentition isasymmetrical. It is difficult to identify each tooth in the larval dentition. In this paper the appearancepattem of tooth germ with developmental process in this fish is described in detail. The formationpattern of the left dentition is contrasted with that of the right one. In the developmental process,the left pharyngeal dentition lacks teeth at position An3. Thus the left dentition is D-type as designatedby Nakajima(1984), while the right one is A-type.
基金supported by grants from the National Key Research and Development Program(2022YFA1104401)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-031 to Z.P.F.)grants from Innovation Research Team Project of Beijing Stomatological Hospital,Capital Medical University(NO.CXTD202204 to Z.P.F.).
文摘Dental mesenchymal stem cells(DMSCs)are pivotal for tooth development and periodontal tissue health and play an important role in tissue engineering and regenerative medicine because of their multidirectional differentiation potential and self-renewal ability.The cellular microenvironment regulates the fate of stem cells and can be modified using various optimization techniques.These methods can influence the cellular microenvironment,activate disparate signaling pathways,and induce different biological effects.“Epigenetic regulation”refers to the process of influencing gene expression and regulating cell fate without altering DNA sequences,such as histone methylation.Histone methylation modifications regulate pivotal transcription factors governing DMSCs differentiation into osteo-/odontogenic lineages.The most important sites of histone methylation in tooth organization were found to be H3K4,H3K9,and H3K27.Histone methylation affects gene expression and regulates stem cell differentiation by maintaining a delicate balance between major trimethylation sites,generating distinct chromatin structures associated with specific downstream transcriptional states.Several crucial signaling pathways associated with osteogenic differentiation are susceptible to modulation via histone methylation modifications.A deeper understanding of the regulatory mechanisms governing histone methylation modifications in osteo-/odontogenic differentiation and immune-inflammatory responses of DMSCs will facilitate further investigation of the epigenetic regulation of histone methylation in DMSC-mediated tissue regeneration and inflammation.Here is a concise overview of the pivotal functions of epigenetic histone methylation at H3K4,H3K9,and H3K27 in the regulation of osteo-/odontogenic differentiation and renewal of DMSCs in both non-inflammatory and inflammatory microenvironments.This review summarizes the current research on these processes in the context of tissue regeneration and therapeutic interventions.
基金Na-tional Natural Science Foundation of China(No.30270652)Fujian Provincial Department of Science and Technology(No.2002I006)
文摘Mammalian tooth development is largely dependent on sequential and reciprocal epithelial-mesenchymal interactions.These processes involve a series of inductive and permissive interactions that result in the determination,differentiation,and organization of odontogenic tissues.Multiple signaling molecules,including BMPs,FGFs,Shh,and Wnt proteins,have been implicated in mediating these tissue interactions.Transcription factors participate in epithelial-mesenchymal interactions via linking the signaling loops between tissue layers by responding to inductive signals and regulating the expression of other signaling molecules.Adult stem cells are highly plastic and multipotent.These cells including dental pulp stem cells and bone marrow stromal cells could be reprogrammed into odontogenic fate and participated in tooth formation.Recent progress in the studies of molecular basis of tooth development,adult stem cell biology,and regene-ration will provide fundamental knowledge for the realization of human tooth regeneration in the near future.
基金supported (in part) by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health
文摘The tooth root cementum is a thin, mineralized tissue covering the root dentin that is present primarily as acellular cementum on the cervical root and cellular cementum covering the apical root. While cementum shares many properties in common with bone and dentin, it is a unique mineralized tissue and acellular cementum is critical for attachment of the tooth to the surrounding periodontal ligament （PDL）. Resources for methodologies for hard tissues often overlook cementum and approaches that may be of value for studying this tissue. To address this issue, this report offers detailed methodology, as well as comparisons of several histological and immunohistochemical stains available for imaging the cementum-PDL complex by light microscopy. Notably, the infrequently used Alcian blue stain with nuclear fast red counterstain provided utility in imaging cementum in mouse, porcine and human teeth. While no truly unique extracellular matrix markers have been identified to differentiate cementum from the other hard tissues, immunohistochemistry for detection of bone sialoprotein （BSP）, osteopontin （OPN）, and dentin matrix protein 1 （DMP1） is a reliable approach for studying both acellular and cellular cementum and providing insight into developmental biology of these tissues. Histoloeical and immunohistochemical aooroaches Drovide insight on developmental biology of cementum.
基金supported by NSFC grant 81371136 to Xue-Dong Zhou, NSFC grant 81470711 to Li-Wei Zheng and grant 2015TD0011 to Ling Ye
文摘Tooth development relies on sequential and reciprocal interactions between the epithelial and mesenchymal tissues, and it is continuously regulated by a variety of conserved and specific temporal-spatial signalling pathways. It is well known that suspensions of tooth germ cells can form tooth-like structures after losing the positional information provided by the epithelial and mesenchymal tissues. However, the particular stage in which the tooth germ cells start to form tooth-like structures after losing their positional information remains unclear. In this study, we investigated the reassociation of tooth germ cells suspension from different morphological stages during tooth development and the phosphorylation of Smad2/3 in this process. Four tooth morphological stages were designed in this study. The results showed that tooth germ cells formed odontogenic tissue at embryonic day （E） 14.5, which is referred to as the cap stage, and they formed tooth-like structures at E16.5, which is referred to as the early bell stage, and E18.5, which is referred to as the late bell stage. Moreover, the transforming growth factor-β signalling pathway might play a role in this process.
基金supported by JSPS KAKENHI from the Japan Society for the Promotion of Science and the Ministry of Education(15H05032 and 15K15752 to Takashi Nakamura and 26253092 to Satoshi Fukumoto)
文摘Tooth crown morphogenesis is tightly regulated by the proliferation and differentiation of dental epithelial cells.Globoside(Gb4),a globo-series glycosphingolipid,is highly expressed during embryogenesis as well as organogenesis,including tooth development.We previously reported that Gb4 is dominantly expressed in the neutral lipid fraction of dental epithelial cells.However,because its functional role in tooth development remains unknown,we investigated the involvement of Gb4 in dental epithelial cell differentiation.The expression of Gb4 was detected in ameloblasts of postnatal mouse molars and incisors.A cell culture analysis using HAT-7 cells,a rat-derived dental epithelial cell line,revealed that Gb4 did not promote dental epithelial cell proliferation.Interestingly,exogenous administration of Gb4 enhanced the gene expression of enamel extracellular matrix proteins such as ameloblastin,amelogenin,and enamelin in dental epithelial cells as well as in developing tooth germs.Gb4 also induced the expression of TrkB,one of the key receptors required for ameloblast induction in dental epithelial cells.In contrast,Gb4 downregulated the expression of p75,a receptor for neurotrophins(including neurotrophin-4)and a marker of undifferentiated dental epithelial cells.In addition,we found that exogenous administration of Gb4 to dental epithelial cells stimulated the extracellular signal-regulated kinase and p38 mitogen-activated protein kinase signalling pathways.Furthermore,Gb4 induced the expression of epiprofin and Runx2,the positive regulators for ameloblastin gene transcription.Thus,our results suggest that Gb4 contributes to promoting the differentiation of dental epithelial cells into ameloblasts.
文摘Tooth tissue engineering is an emerging biotechnique that will provide replacemental teeth for patients suffering from different diseases causing tooth loss. Although some attempts have been tried to generate whole tooth both in vivo and in vitro, the lack of the knowledge for tooth initiation and development, as well as for tooth shape controlling mechanisms greatly impede the progress of this technique. This article reviewed and discussed some recent findings in tooth tissue engineering related to the cell resource, the concept of reconstruction and regeneration, the application of artificial scaffolds, together with the methods of organ culture and implantation.
基金supported by National Nature Science Foundation of China(Project No.3057 2046,30725042)
文摘Aim To characterize the odontogenic capability of apical bud and phenotypical change of apical bud cells （ABCs） in different microenvironment.Methodology Incisor apical bud tissues from neonatal SD rat were dissected and transplanted into the renal capsules to determine their odontogenic capability. Meanwhile ABCs were cultured and purified by repeated differential trypsinization. Then ABCs were cultured with conditioned medium from developing apical complex cells （DAC-CM）. Immunocytochemistry, reverse transcriptase polymerase chain reaction （RT-PCR） and scanning electron microscope （SEM） were performed to compare the biolo- gical change of ABC treated with or without DAC-CM. Results First we confirmed the ability of apical bud to form crown-like structure ectopically. Equally important, by using the developing apical complex （DAC） condi- tioned medium, we found the microenvironment created by root could abrogate the ＂crown＂ features of ABCs and promote their proliferation and differentiation. Conclusion ABCs possess odontogenic capability to form crown-like tissues and this property can be affected by root-produced microenvironment.
