EV Modulates Osteogenic differentiation in hPDL-MSCs
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE312257 | GEO | 2026/07/15
REPOSITORIES: GEO
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Project description:Periodontal homeostasis is maintained by a delicate balance between tissue regeneration and degradation, orchestrated through complex regulatory networks of cellular and molecular signaling. miRNAs act as pivotal post-transcriptional regulators that fine-tune these signaling cascades. Despite increasing recognition of their regulatory potential, the specific miRNAs governing stem cell maintenance and differentiation in the periodontium remain insufficiently defined. In this study, we identified hsa-181c-5p and hsa-let-7c-3p within the extracellular vesicles secreted from human periodontal ligament mesenchymal stem cells (hPDL-MSCs) as a candidate regulator contributing to PDL-MSC homeostasis. hsa-let-7c-3p promotes the proliferation and migration while suppressing osteogenic differentiation of hPDL-MSCs. In the meanwhile, miR-181c-5p was consistently upregulated in hMSCs during osteogenesis, and its gain- and loss-of-function produced concordant effects. Integrative analyses combining AGO2-based immunoprecipitation sequencing (RIP-Seq), RNA-Seq, dual-luciferase reporter, and western blot identified miRISC-mediated targetome of miRNAs. Collectively, our study unveiled novel miRNA-mRNA networks through which hPDL-MSC–derived EVs affecting osteogenic differentiation and proliferation, providing new mechanistic insight into miRNA-mediated stem cell regulation and periodontal regeneration.
2026-07-15 | GSE311799 | GEO
Project description:Mesenchymal stem cells (MSCs) isolated from human gingival tissue and periodontal ligament (PDL) have shown potential for periodontal regeneration. Although PDL-MSCs have been recognized as the best choic for cell-based periodontal regeneration, isolation of PDL-MSCs required tooth extraction which is impractical for clinical use. Supracrestal gingival connective tissue (SG) is a part of gingival tissue which located closely to PDL and can be harvested without tooth extraction. Here, the characteristics of MSCs derived from SG was evaluated. Differential gene expression profiles of hSG-MSCs, hPDL-MSCs, and human marginal gingival tissue (MG)-derived MSCs were compared. Results demonstrated that hSG-MSCs had a more similar gene expression profile to the hPDL-MSCs than the hMG-MSCs, suggested a potential candidate cell source of SG for future peridontal tissue engineering.
2022-12-05 | GSE198663 | GEO
Project description:Functional recovery of the periodontium remains a major clinical challenge. To harness the therapeutic potential of extracellular vesicles (EVs) derived from human periodontal ligament mesenchymal stem cells (hPDL-MSC), we identified and characterized the encapsulated miR-378a as a pivotal regulator associated with osteogenic commitment. hPDL-MSC and derivative EVs were dynamically examined throughout osteogenesis, revealing a temporal and progressive enrichment pattern. Mechanistically, integrative microarray, RNA sequencing, bioinformatic analysis, and functional assays established PIM2 and DAZAP2 as direct targets of miR-378a. Overexpression of miR-378a post-transcriptionally suppressed DAZAP2, leading to enhanced nuclear translocation of phosphorylated-SMAD1/5/9 and subsequent activation of canonical BMP signaling. Rescue experiments reinforced the essential role of the miR-378a–DAZAP2–SMAD axis in osteogenic differentiation. Collectively, our findings delineate the molecular pathway triggered by hPDL-MSC-derived exosomal miR-378a and provide new mechanistic insights into EV-mediated modulation of stem cell fate.
2026-02-26 | GSE320570 | GEO
Project description:The periodontal ligament (PDL), which connects the teeth to the alveolar bone, is essential for periodontal tissue homeostasis. Although the significance of the PDL is recognized, molecular mechanisms underlying PDL function are not well-known. We report that Mohawk homeobox (Mkx), a tendon-specific transcription factor, regulates PDL homeostasis by preventing its degeneration. Mkx is expressed in the mouse PDL at the age of 10 weeks and 12 months. In Mkx-/- mice, age-dependent expansion of the PDL at the maxillary 1st molar (M1) furcation area was observed. Transmission electron microscopy (TEM) revealed that Mkx-/- mice presented collagen fibril degeneration in PDL with age, while the collagen fibril diameter gradually increased in Mkx+/+ mice. PDL cells lost their shape in Mkx-/- mice, suggesting changes in PDL properties. Microarray and quantitative polymerase chain reaction (qPCR) analyses of Mkx-/- PDL revealed an increase in osteogenic gene expression and no change in PDL- and inflammatory-related gene expression. Additionally, COL1A1 and COL1A2 were upregulated in Mkx-overexpressing human PDL fibroblasts, whereas osteogenic genes were downregulated. Our results indicate that Mkx prevents PDL degeneration by regulating osteogenesis. Mohawk transcription factor is essential for homeostasis of the periodontal ligament by regulating osteogenic changes with age.
2017-01-17 | GSE92331 | GEO
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.
2022-09-28 | GSE197828 | GEO
Project description:Purpose : This study was performed to investigate the changes in gene expression in periodontal ligament (PDL) cells between normal occlusal function and hypofunction through RNA sequencing and elucidate the related role in maintaining the PDL homeostasis. Method : Premolars extracted for orthodontic treatment were used. The teeth with occlusal contact for control group (n=17), teeth without occlusal contact for experienment group (n=17). After the PDL cells were isolated from the extracted teeth, differentially expressed gene (DEG) analysis, and real-time PCR were performed to compare the two groups. The effect of Bardet-Biedl syndrome 7 (BBS7) knockdown was evaluated by RT-qPCR, Wound healing assay, and Tubule formation assay. Result : We detected that the expression of BBS7 was downregulated in occlusal hypofunctional PDL through RNA-sequencing. Sonic Hedgehog signaling (Shh) activity was closely associated with BBS7 expression in periodontal ligament cells. In addition, the cell migration and angiogenesis were also suppressed by BBS7 knockdown in vitro. Conclusion : We suggest that BBS7 plays an essential role in maintaining Shh signaling activity for PDL homeostasis.
2021-11-23 | GSE189288 | GEO
Project description:We employed a cell sequencing approach using 10x Genomics scRNA-seq to study the genetic profiling of LepR+ cells in the periodontal ligament (PDL). It has been suggested that PDL-derived LepR+ cells maintain hard tissue homeostasis by differentiating into hard tissue-forming cells such as osteoblasts and cementoblasts. In this study, we generated LepR-cre; R26-tdTomato; Runx2-GFP mice, and performed scRNAseq using their PDL cells. This study is the first genetic profiling of a LepR-cre-labeled population in PDL.
2025-08-12 | GSE288734 | GEO
Project description:Human periodontal ligament (HPDL) is continuously exposed to mechanical stress in vivo. In this study, in utilizing DNA chips, we analyzed the influences of mechanical stress on the gene expression profile of HPDL cells in vitro. HPDL cells were obtained from extracted first premolars of individuals undergoing tooth extraction for orthodontic treatment. Then, HPDL cells were applied to a stretch apparatus. They were constantly stretched and relaxed at 0.5 Hz for 48hr with 110ï¼ force elongation. After the application of the cyclic tension force, total RNA was extracted. Then, in utilizing the DNA chips (Human Oligo 30K DNA Chip containing almost all human genes in the genome). We analyzed the differences of gene expression between the stretched and the non-stretched control HPDL cells The DNA chip analysis identified 17 up-regulated genes that showed at least 2-fold difference in their relative intensities between the stretched and the control. This result included the genes for the glutamate receptor binding protein: HOMER1, for the growth factor receptor: CNTFR, for the ECM remodeling protein: MMP15, for the protein interacting with calcineurin A: DSCR1, for the cytoskeletal protein: LRRFIP1, for the glutamate receptor: GRIN3A and some novel genes. On the basis of these data, we suggest that mechanical stress, in other words in vivo occlusal force, may affect the functions of HPDL cells Gene expression profiles were constructed using Human Oligo DNA Chip 30K (Hitachi software engineering) in human periodontal ligament cells (The 48-h stretched and the 48-h non-stretched, control).
2010-06-19 | E-GEOD-19118 | biostudies-arrayexpress
Project description:Periodontal ligament stem cells (PDLSCs) play central roles in periodontal ligament (PDL) tissue homeostasis, repair, and regeneration. Previously, we established a protocol to differentiate human induced pluripotent stem cell-derived neural crest-like cells (iNCs) into PDLSC-like cells (iPDLSCs) using human PDL cell-derived extracellular matrix (ECM). However it remained unclear what factors principally regulate the differentiation of iNCs into iPDLSCs. In this study, we aimed to identify the transcription factor regulating production of human PDL cell-derived ECM, which is responsible for the generation of iPDLSCs. We cultured iNCs on two human PDL cell lines (HPDLC-3S and HPDLC-3U) and human dermal fibroblasts (HDF). iNCs cultured on HPDLC-3U showed higher iPDLSC-associated gene expression and mesenchymal differentiation capacity than cells cultured on HDF or HPDLC-3S. The transcription factor PAX9 was highly expressed in HPDLC-3U compared with HDF and HPDLC-3S. iNCs cultured on siPAX9-transfected HPDLC-3U displayed downregulation of iPDLSC-associated marker expression and adipocytic differentiation capacity relative to controls. Our findings suggest that PAX9 is one of the transcription factors regulating ECM production in human PDL cells, which is responsible for the differentiation of iNCs into iPDLSCs.
2022-07-18 | GSE208250 | GEO
Project description:The aim of this study was to evaluate and compare the gene expression profiles of dental follicle and periodontal ligament in humans, which can possibly explain their functions of dental follicle and PDL such as eruption coordination and stress resorption. That may apply this information to clinical problem like eruption disturbance and to periodontal tissue engineering. PDL samples were obtained from permanent premolars (n=11) and dental follicle samples were obtained during extraction of supernumerary teeth (n=4). Comparative cDNA microarray analysis revealed several differences in gene expression between permanent PDL and dental follicles.
2014-08-21 | E-GEOD-51342 | biostudies-arrayexpress