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Consequences of decreased TNAP activity during osteogenic differentiation of periodontal ligament cells – a new model for dental defects in hypophosphatasia

ABSTRACT: Consequences of decreased TNAP activity during osteogenic differentiation of periodontal ligament cells – a new model for dental defects in hypophosphatasia

PROVIDER: PRJNA543291 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9071690.fastq.gz	Fastqsanger.gz
	SRR9071691.fastq.gz	Fastqsanger.gz
	SRR9071692.fastq.gz	Fastqsanger.gz
	SRR9071683.fastq.gz	Fastqsanger.gz
	SRR9071684.fastq.gz	Fastqsanger.gz

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Consequences of decreased TNAP activity during osteogenic differentiation of periodontal ligament cells – a new model for dental defects in hypophosphatasia

Project description:The effects of TNAP inhibition with levamisole during osteogenic differentiation were analyzed in primary human periodontal ligament cells since patients suffering from hypophosphatasia often display dental symptoms.

2020-04-30 | GSE131338 | GEO

Differentially expressed long noncoding RNA expression between periodontal ligament stem cells from healthy periodontal tissue and periodontal ligament stem cells from inflammatory periodontal tissue.

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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Diminished osteogenic capacity in mature periodontal ligament stem cells via RELB downregulation

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.

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Comprehensive analysis of M2 macrophage-derived exosomes facilitating osteogenic differentiation of human periodontal ligament stem cells

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.

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H3K27me3Alpha-Ketoglutarate Drives an Osteogenic and Extracellular Matrix Gene Program in Periodontal Ligament Fibroblasts via Selective Reduction of H3K27me3 [RNA-Seq]

Project description:Periodontal disease is a chronic inflammatory condition that destroys tooth-supporting tissues, particularly alveolar bone and the periodontal ligament, and effective regenerative therapies remain limited. While the role of metabolic-epigenomic crosstalk in determining cell fate is well established, the specific mechanism by which a tricarboxylic acid (TCA) cycle metabolite can modulate chromatin regulation to promote periodontal regeneration remains to be elucidated. The impact of one TCA-cycle metabolite, alpha-ketoglutarate (α-KG), was examined in human periodontal ligament fibroblasts cultured under osteogenic induction and profiled by ALP assays, RT-qPCR, analyses of multiple histone modifications, ATAC-seq, and RNA-seq. α-KG increased ALP activity and up-regulated genes associated with osteogenesis and the extracellular matrix (ECM). ATAC-seq revealed minimal genome-wide accessibility changes, whereas histone analyses showed reduced H3K27me3, consistent with an epigenetic mechanism that does not require extensive chromatin opening. The RNA-seq identified α-KG-induced 14 genes upregulated, including multiple components of the OGN-OMD-PLAP1/ASPN-ECM2 locus, supporting an osteogenic/ECM transcriptional program. In a mouse periodontal regeneration model, oral administration of α-KG enhanced alveolar bone regeneration and reduced H3K27me3 signals and collagen-rich tissue organization within the periodontal ligament space. These findings identify α-KG as a metabolite-driven epigenetic modulator that alleviates H3K27me3-mediated repression and supports periodontal regeneration.

2026-01-16 | GSE316449 | GEO

H3K27me3Alpha-Ketoglutarate Drives an Osteogenic and Extracellular Matrix Gene Program in Periodontal Ligament Fibroblasts via Selective Reduction of H3K27me3 [ATAC-Seq]

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Dynamic proteomic profiling of human periodontal ligament stem cells during osteogenic differentiation

Project description:Human periodontal ligament stem cells (hPDLSCs) are ideal seed cells for periodontal regeneration. To better understand the dynamic protein profiles during hPDLSCs osteogenic differentiation, we conducted a quantitative proteomics to reveal the temporal protein expression pattern during this process. Clustering and functional annotation by Gene Ontology terms identified distinctions among proteins with different dynamic tendencies. Pathway enrichment analysis with the Kyoto Encyclopedia of Genes and Genomes database found that oxidative phosphorylation (OXPHOS) was significantly involved, which further predicted continuous activation by Ingenuity Pathway Analysis software. Redox-sensitive signalling pathways with dynamic activation status showed associations with OXPHOS to various degrees, especially the sirtuin signalling pathway. SOD2, an important component of the sirtuin signalling pathway, is a hub protein of the interaction network and displays a persistent increase during osteogenesis. Our in-depth dynamic proteomic analysis indicated the comprehensive and dynamic regulation mechanism during hPDLSC osteogenesis.

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Expression data from human periodontal ligament

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

2011-03-17 | E-GEOD-27993 | biostudies-arrayexpress

Cyclic stretch-induced exosomes from periodontal ligament cells promote osteoblasts osteogenic differentiation via the miR-181d-5p/TNF signaling pathway

Project description:Objective: To investigate the effects of stretch-induced periodontal ligament cell (PDLC) exosomes on osteoblast differentiation, and to explore their regulatory role in mechanical force-related periodontal tissue remodeling.Design: After applying 20% stretch loading to human periodontal ligament cells, exosomes were extracted from the supernatant and co-cultured with osteoblasts to detect their effects on osteogenic differentiation. Meanwhile, the exosomes were sequenced by high-throughput microRNA sequencing for bioinformatic analysis and validation to explore exosome signaling pathways through miRNAs.Results: Stretch-induced PDLC exosomes could be taken up by osteoblasts and promoted osteogenic differentiation of osteoblasts, as demonstrated by the increased expression levels of osteogenesis-related factors and enhanced ALP staining. In the miRNA profile of differentially expressed PDLC exosomes under stretch loading, miRNA-181d-5p was up-regulated significantly. The expression levels of osteogenesis-related factors and ALP staining were also increased in osteoblasts transfected with miR-181d-5p, and this effect might be related to the inhibitory role of exosomal miR-181d-5p on tumor necrosis factor (TNF).Conclusions: Stretch-induced PDLC exosomes exhibited a promoting effect on osteogenic differentiation, which might result from the inhibition of TNF via exosomal miR-181d-5p.

2023-10-30 | GSE245304 | GEO

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