Notch signaling controls periodontal ligament maturation through regulating Lamin A
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA531429 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8865160.fastq.gz | Fastqsanger.gz | |||
| SRR8865240.fastq.gz | Fastqsanger.gz | |||
| SRR8865161.fastq.gz | Fastqsanger.gz | |||
| SRR8865241.fastq.gz | Fastqsanger.gz | |||
| SRR8865162.fastq.gz | Fastqsanger.gz |
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Project description:Tooth eruption is a continuous biological proces with dynamic changes at cellular and tissue levels particularly within the periodontal ligament (PDL). Occlusion completion is a significant physiological landmark of dentintion establishment. However the implication and molecular networks engaging in of this event on the the final PDL maturation are still largely unknown. In this study, using rat and mouse molar teeth and transgenic approaches, as well as a human PDL cell line by combining RNAseq and proteomic analysis systematically, we screened the key molecular links in regulating PDL maturation before and after occlusion establishiment. We discovered Notch, a key molecular pathway in regulating stem cell fate and differentiation, is a major player in the event. Intercepting Notch pathway by deleting its key canonical transtripitonal factor: RBP-Jkappa using conditional knocking out strategy in the mice delayed PDL maturation. We also identified that Lamin A, a cell nuclear lamina member, is one unique marker of PDL maturation and its expression is under the control of Notch signalling. Our study therefore provides a deep insight of how PDL maturation is regulated molecularly and we expect the outcomes to be applied to better understand the molecular regulation networks and physiological conditions such as tooth eruption and movement, and also for periodontal diseases.
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Project description:Periodontitis can impair the osteogenic differentiation of human periodontal mesenchymal stem cells, but the underlying molecular mechanisms are still poorly understood. Long noncoding RNAs (lncRNAs) have been demonstrated to play significant roles under both physiologic and pathological conditions. We performed comprehensive lncRNAs profiling by lncRNA microarray to identify differentially expressed long noncoding RNA expression between Periodontal ligament stem cells from healthy Periodontal tissue and periodontal ligament stem cells from inflammatory periodontal tissue. Our analysis identified 233 lncRNAs and 423 mRNAs that were differently expressed (fold change >2.0, p-value < 0.05) between the two groups of cells. The GO analysis revealed that the significantly down-regulated biological processes included multicellular organismal process, developmental process and multicellular organismal development and the significantly up-regulated biological processes included cellular process, biological regulation and response to stimulus in periodontal ligament stem cells from inflammatory periodontal tissue. The Pathway analysis revealed that the differentially expressed mRNAs may involved in Focal adhesion, ECM-receptor interaction, Bacterial invasion of epithelial cells, Long-term depression, Circadian entrainment and HIF-1 signaling pathway. Two-condition experiment, periodontal ligament stem cells from healthy periodontal tissue (hPDLSCs) vs. periodontal ligament stem cells from inflammatory periodontal tissue (pPDLSCs), Biological replicates: 3 control replicates (hPDLSCs), 3 testing replicates (pPDLSCs).
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Project description:We used microarrays to detect the differences in gene-expression of the periontal ligament between patients with healthy periodontal ligament and patients with periodontitis RNA was extracted directly from the middle third of the human periodontal ligament
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Project description:The pre-occlusal eruption brings the rat molars into functional occlusion, which implicates tensional strains during mastication. We hypothesized that upon establishment of occlusion, the periodontal ligament undergoes cell and extracellular matrix maturation to adopt to this mechanical function. We thus aimed to characterize the protein content and changes in expression levels of tensionally relevant extracellular matrix components in the periodontal ligament between the eruption and newly established occlusion in rat molars. Twelve Wistar male rats were divided into 3 groups based on eruption and occlusal stages: covering the pre-occlusal stages at time of eruption, the first day of occlusion and 1 week after occlusion. We employed laser capture microdissection to obtain samples of the periodontal ligament at three regions, cervical, apical and subapical. The proteome was screened with Tandem Mass Tag 10-plexTM mass spectrometry and the expression of key proteins were confirmed by immunofluorescence. Differential expression of matrisome proteins was seen in the cervical and the apical region. Downregulation of pro-metabolic proteins, such as apolipoproteins implicated in lipid transport was observed. Alpha-fetoprotein, a stem cell marker, was also downregulated indicating cell differentiation and PDL maturation. Upregulated proteins were components of the extracellular matrix, involving several proteoglycans and glycoproteins and the matrisome was thus further analyzed. Periostin appeared around collagen α-1 (III) fibers and its expression was particularly strong on Sharpey’s fibers. This co-localization coincided with organization of collagen fibers in direction of the occlusal forces. Establishment of occlusion coincides with cellular differentiation and the maturation of the extracellular matrix of the periodontal ligament, as seen by downregulation of the stem cell marker Alpha-fetoprotein and apolipoproteins, and the progressive accumulation of collagen type III fibers, proteoglycans, glycoproteins. The increase in collagen fiber associates periostin may reflect a physiological response to enforce cell-ECM contacts during PDL maturation.
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Project description:Periodontal tissue supports teeth in the alveolar bone socket via fibrous attachment of the periodontal ligament (PDL). The PDL contains many stromal cell types, including osteoblasts, cementoblasts, periodontal fibroblasts, and stem/progenitor cells. However, the characteristics and lineage hierarchy of each cell type remain poorly defined. Here we present a single-cell atlas of PDL, highlighting diverse cell populations in PDL.
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