Transcriptomic Profiling of Stromal Cell-derived Factor-1 and Exendin-4 Treated Periodontal Ligament Stem Cells Undergoing Osteogenic Differentiation by RNA-Seq
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE163354 | GEO | 2021/04/20
REPOSITORIES: GEO
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Project description:Although periodontal ligament stem cells (PDLSCs) are pivotal for periodontal tissue regeneration, their regenerative capacity diminishes with the PDL maturity. This study aims to elucidate the mechanisms underlying this phenomenon.Single-cell RNA sequencing (scRNA-seq) was conducted on immature and mature human PDL tissues to characterize the heterogeneity and predict critical regulators affecting osteogenic capacity of PDLSCs. Subsequently, the predicted role of RELB was experimentally validated both in vitro and in vivo using small interfering RNA.Our scRNA-seq analysis revealed significant heterogeneity within the PDLSC population. Notably, PDLSC-5 subtype, which exhibited osteogenic potential and positioned at the terminus of the pseudotime trajectory, was markedly reduced in mature PDL tissues. RELB was specifically overexpressed in PDLSC_5 and identified as a key transcription factor (TF) for this subcluster. Knockdown of RELB significantly inhibited the osteogenic differentiation capacity of PDLSCs in vitro and bone formation potential in vivo at both developmental stages. This inhibitory effect appears to be mediated, at least in part, through the downregulation of its target gene, superoxide dismutase 2 (SOD2).This study demonstrates that the proportion of PDLSCs with osteogenic ability significantly declines with maturity, accounting for the diminished regeneration capacity of mature periodontal tissue. Furthermore, RELB was identified as a crucial TF for maintaining the osteogenic potential of PDLSCs. These findings provide a theoretical basis for strategies aimed at optimizing the bone regeneration capacity of PDLSCs.
2025-09-04 | GSE306722 | GEO
Project description:As the primary seed cells in periodontal tissue engineering, the role of periodontal ligament stem cells (PDLSCs) in periodontal tissue regeneration and bone remodeling during orthodontic tooth movement (OTM) has been well documented. Nevertheless, the impact of different polarization states of macrophages on the osteogenic differentiation of PDLSCs is poorly understood. M0, M1 and M2 macrophage-derived exosomes (M0-exo, M1-exo and M2-exo) were treated with primary cultured human PDLSCs, respectively. Identification of differentially expressed microRNAs (DE-miRNA) in M0-exo and M2-exo by miRNA microarray. In summary, we have indicated for the first time that M2-exo can promote osteogenic differentiation of human PDLSCs, and have revealed the functions and pathways involved in the DE-miRNAs of M0-exo and M2-exo and their downstream targets.
2022-10-31 | GSE209957 | GEO
Project description:Cell-based therapies using periodontal ligament stromal cells (PDLSC) for periodontal regeneration may represent an alternative source for mesenchymal stromal cells (MSC) to MSC derived from bone marrow (MSC(M)) and adipose tissue (MSC(AT)). We aimed to characterize the osteogenic/periodontal potential of PDLSC in comparison to MSC(M) and MSC(AT). PDLSC were obtained from surgically extracted healthy human third molars, while MSC(M) and MSC(AT) were obtained from a previously established cell bank. Flow cytometry, immunocytochemistry, and cell proliferation analyses provided cellular characteristics from each group. Cells from the three groups presented MSC-like morphology, MSC-related marker expression, and multilineage differentiation capacity (adipogenic, chondrogenic, and osteogenic). In this study, PDLSC expressed osteopontin, osteocalcin, and asporin, while MSC(M) and MSC(AT) did not. Of note, only PDLSC expressed CD146, a marker previously applied to identify PDLSC, and presented higher proliferative potential compared to MSC(M) and MSC(AT). Upon osteogenic induction, PDLSC exhibited higher calcium content and enhanced upregulation of osteogenic/periodontal genes compared to MSC(M) and MSC(AT), such as Runx2, Col1A1 and CEMP-1. However, the alkaline phosphatase activity of PDLSC did not increase. Our findings suggest that PDLSC might be a promising cell source for periodontal regeneration, presenting enhanced proliferative and osteogenic potential compared to MSC(M) and MSC(AT).
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Project description:To study the molecular mechanisms underlying PDLSC osteogenic differentiation, we developed RNA sequencing with Illumina HiSeq2000 to comprehensively identify RNA expression profiles in normal PDLSCs, osteogenic inductive PDLSCs and mechanical force-induced PDLSCs. Plenty of RNAs were found to be differentially expressed by RNA sequencing. Furthermore, the potential functions of these RNAs were investigated using bioinformatic analysis.
2018-03-09 | GSE106887 | GEO
Project description:This study investigated the cellular response of human periodontal ligament stem cells (PDLSCs) to elevated levels of a specific fatty acid (FA), namely, palmitic acid (PA) and the role of long noncoding RNAs (lncRNAs) in regulating PA exposure-compromised osteogenic potential of PDLSCs. It was found that exposure of PDLSCs to abundant PA led to decreased osteogenic differentiation of cells. Through microarray analysis and gain/loss-of-function studies, AC018926.2 was identified and validated as the lncRNA that was most sensitive to PA and a regulator in the process of PDLSC osteogenic differentiation under a PA condition. Then, RNA sequencing and KEGG analysis demonstrated that AC018926.2 upregulated integrin α2 (ITGA2) expression at the transcriptional level and therefore activated ITGA2/FAK/AKT signaling. Further functional studies revealed that inactivation of ITGA2/FAK/AKT signaling by silencing ITGA2 counteracted the enhancement of the PDLSC osteogenic potential induced by AC018926.2 overexpression. Moreover, the results of bioinformatics analysis and the RNA immunoprecipitation (RIP) assay suggested that AC018926.2 might transcriptionally regulate ITGA2 expression by binding to poly (ADP-ribose) polymerase 1 (PARP1). Our data suggest that AC018926.2 plays a crucial role in PA exposure-compromised osteogenic potential of PDLSCs.
2022-11-26 | GSE218434 | GEO
Project description:Stromal cell-derived factor-1 (SDF-1) and Exendin-4 (EX-4) play beneficial roles in promoting periodontal ligament stem cells (PDLSCs) osteogenic differentiation, while the detailed mechanism has not been clarified. In this study, we aimed to evaluate the biological mechanism of SDF-1 and EX-4 alone or synergistic application in regulating PDLSCs differentiation by RNA-sequencing (RNA-seq). A total of 110, 116 and 109 differentially expressed genes (DEGs) were generated in osteogenic medium induced PDLSCs treated by SDF-1, EX-4, and SDF-1+EX-4, respectively. The DEGs in SDF-1 group were enriched in signal transduction related signaling pathways; the DEGs in EX-4 group were enriched in metabolism and biosynthesis-related pathways; and the DEGs generated in SDF-1+EX-4 group were mainly enriched in RNA polymerase II transcription, cell differentiation, chromatin organization, protein phosphorylation pathways. Based on Venn analysis, a total of 37 specific DEGs were identified in SDF-1+EX-4 group, which were mainly enriched in negative regulation of autophagy and cellular component disassembly signaling pathways. Short time-series expression miner (STEM) analysis grouped all expressed genes of PDLSCs into 49 clusters according to the dynamic expression patterns and 25 genes, including NRSN2, CHD9, TUBA1A, distributed in 10 gene clusters in SDF-1+EX-4 treated PDLSCs were significantly up-regulated compared with the SDF-1 and EX-4 alone groups. The gene set enrichment analysis indicated that SDF-1 could amplify the role of EX-4 in regulating varied signaling pathways, such as type II diabetes mellitus and insulin signaling pathways; while EX-4 could aggravate the effect of SDF-1 on PDLSCs biological roles via regulating primary immunodeficiency, tight junction signaling pathways. In summary, our study confirmed that SDF-1 and EX-4 combined application could enhance PDLSCs biological activity and promote PDLSCs osteogenic differentiation by regulating the metabolism, biosynthesis and immune-related signaling pathways.
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Project description:Periodontal ligament stem cells (PDLSCs) are optimal seed cells for periodontal regeneration; thus, exploration of the mechanisms regulating PDLSCs osteogenic differentiation is critical. Here, tandem mass tag quantitative proteomics and phosphoproteomic analyses of human PDLSCs were carried out after osteogenic differentiation for 14 days. Proteomic analyses identified 314 differentially expressed proteins (DEPs) that were predicted to be mostly extracellular. Gene ontology and pathway enrichment analyses revealed that the mineral absorption signaling pathway was significantly involved. For phosphoproteomics, un-normalized data identified 1016 differentially expressed phosphorylation sites (DEPSs) corresponded to 380 DEPs, whereas in normalized data, 3030 DEPSs were identified, corresponding to 358 DEPs. Overlapping of these data identified 16 phosphorylated DEPs, among which tetratricopeptide repeat protein 17, stanniocalcin-1, and extracellular superoxide dismutase [Cu-Zn] were significantly related. Kyoto
2022-02-25 | PXD031905 |
Project description:Dental stem cells isolated from oral tissues have been shown to provide with high proliferation ability and multi-lineage differentiation potential. Although the dental stem cells possess the potential of nerve regeneration, the specific expression profile of dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) are still unclear. Here, DPSCs and PDLSCs, collected from the same tooth with 3 donors, were tested for high-throughput protein profiles by combining two-dimensional gel proteomics and TMT-based proteomics.
2021-06-10 | PXD021997 | Pride
Project description:Periodontal ligament (PDL) stem-like cells (PDLSCs) are considered to be promising for the regeneration of periodontium because they demonstrate multipotency, high proliferative capacity, and potential to regenerate bone, cementum, and PDL tissue. However, the transplantation of autologous PDLSCs is restricted by limited availability and the need for tooth extraction to isolate these cells. PDLSCs are derived from neural crest cells (NCs) in early vertebrate development and NCs persist in adult PDL tissue. Therefore, we devised to promote the regeneration of periodontium by activating NCs to differentiate into PDLSCs and increasing their total number. SK-N-SH cells cultured on the extracellular matrix derived of human PDL cells (SK-PDLSCs) strongly expressed PDL-related marker genes and highly differentiated into mesenchymal lineage cells compared to untreated SK-N-SH cells. Expression levels of various hyaluronic acid (HA)-related genes were upregulated in induced pluripotent stem cells (iPSCs)-derived PDLSCs and SK-PDLSCs compared to iPSCs-derived NCs and SK-N-SH cells, respectively. Magnetic-activated cell sorting-assisted CD44-positive enrichment population of SK-N-SH cells showed higher expression of PDL-related marker genes after SK-PDLSCs induction than the CD44-negative population. Knockdown of CD44 in SK-N-SH cells significantly inhibited their ability to differentiate into SK-PDLSCs, while lower molecular HA (LHA) induction enhanced SK-PDLSC differentiation. LHA-containing electrospun nanofibrous membranes also promoted their SK-PDLSC differentiation. Our findings suggest that SK-N-SH cells are applied as a new model to induce the differentiation of NCs into PDLSCs. The LHA-CD44 relation is important for the differentiation of NCs into PDLSCs. LHA-containing electrospun nanofibrous membranes would promote the regeneration of periodontium by activating NCs in PDL tissue and increasing the total number of PDLSCs.
2023-06-27 | GSE235864 | GEO
Project description:ObjectivesStromal cell-derived factor-1 (SDF-1) actively directs endogenous cell homing. Exendin-4 (EX-4) promotes stem cell osteogenic differentiation. Studies revealed that EX-4 strengthened SDF-1-mediated stem cell migration. However, the effects of SDF-1 and EX-4 on periodontal ligament stem cells (PDLSCs) and bone regeneration have not been investigated. In this study, we aimed to evaluate the effects of SDF-1/EX-4 cotherapy on PDLSCs in vitro and periodontal bone regeneration in vivo.MethodsCell-counting kit-8 (CCK8), transwell assay, qRT-PCR and western blot were used to determine the effects and mechanism of SDF-1/EX-4 cotherapy on PDLSCs in vitro. A rat periodontal bone defect model was developed to evaluate the effects of topical application of SDF-1 and systemic injection of EX-4 on endogenous cell recruitment, osteoclastogenesis and bone regeneration in vivo.ResultsSDF-1/EX-4 cotherapy had additive effects on PDLSC proliferation, migration, alkaline phosphatase (ALP) activity, mineral deposition and osteogenesis-related gene expression compared to SDF-1 or EX-4 in vitro. Pretreatment with ERK inhibitor U0126 blocked SDF-1/EX-4 cotherapy induced ERK signal activation and PDLSC proliferation. SDF-1/EX-4 cotherapy significantly promoted new bone formation, recruited more CXCR4+ cells and CD90+ /CD34- stromal cells to the defects, enhanced early-stage osteoclastogenesis and osteogenesis-related markers expression in regenerated bone compared to control, SDF-1 or EX-4 in vivo.ConclusionsSDF-1/EX-4 cotherapy synergistically regulated PDLSC activities, promoted periodontal bone formation, thereby providing a new strategy for periodontal bone regeneration.
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