ArticleJournal of advanced research2025
Multi-omics approach reveals TGF-β signaling-driven senescence in periodontium stem cells.
Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Key molecular networks underlying retinol's biphasic effects on cell proliferation through multi-omics integrative analysis using genome-scale metabolic modeling.Synthetic and systems biotechnology · 2027Article
- Review
- Body roundness index as a novel marker of periodontitis in US adults: NHANES 2009-2014 analysis.Medicine · 2026Article
- [Oral Aging: Age-Related Changes and Their Association With Systemic Aging].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2026Review
- Mitochondrial Regulation of Periodontal Ligament Stem Cell Fate and Function.Stem cell reviews and reports · 2026Review
- Advances in Oral Cavity Stem Cell Research Revealed through Multi-omics Analysis.Stem cell reviews and reports · 2026Review
- SATB1 regulates the osteogenic differentiation of PDLSCs via HDAC1 mediated non-histone protein deacetylation and ubiquitination mechanism and through p38 MAPK pathway under hydrogen peroxide-induced senescent conditions.Stem cell research & therapy · 2026Article
- ROS Activated NETosis of Bone Marrow CD55Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Biological mechanisms governing the periodontal regenerative microenvironment: cellular crosstalk, extracellular matrix remodelling, and immunomodulation.Frontiers in cell and developmental biology · 2026Review
- The drug discovery and therapeutic nano-strategies targeting cellular senescence.Materials today. Bio · 2025Review
- Berbamine Targets TNFAIP3: A Bioactive Compound Alleviates Oxidative Stress and Inflammation in the Comorbidity of Insomnia and Chronic Obstructive Pulmonary Disease Through Multi-Omics Integration.International journal of molecular sciences · 2025Article
- Canagliflozin improves high-salt-induced aortic arteriosclerosis and premature aging in dahl salt-sensitive rats through the SIRT6/HIF-1 α signaling pathway.Molecular and cellular biochemistry · 2025Article
- Metabolic regulation in the senescence process of stem cells.Stem cells translational medicine · 2025Review
- Differentiated muscle cells of salamander Pleurodeles waltl re-enter the cell cycle.Histochemistry and cell biology · 2025Article
- Histological and immunohistochemical analysis of human periapical lesions: a study of TGF-β1 and CD68 markers.BMC oral health · 2025Article
- Editorial: Perivascular niche and stem cell signaling in tooth.Frontiers in cell and developmental biology · 2025Article
- Regulation and functional importance of human periodontal ligament mesenchymal stromal cells with various rates of CD146+ cells.Frontiers in cell and developmental biology · 2025Article
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThe periodontal ligament (PDL), a dynamic connective tissue that anchors teeth to the alveolar bone, enables tooth retention and facilitates continuous turnover. The integrity of the periodontium is maintained by periodontal ligament stem cells (PDLSCs), whose dysfunction and senescence with age can disrupt tissue homeostasis, hinder injury repair, and lead to tooth loss, ultimately impacting overall health. Transforming growth factor-β1 (TGF-β1) is known for its regenerative properties and as a functional paracrine factor in stem cell therapy, but its precise role in modulating PDLSC activity remains controversial and poorly understood.
objectivesThis study aims to clarify the role of TGF-β1 in PDLSC senescence and identify the underlying molecular mechanisms, thereby advancing our understanding of age-related periodontal diseases and informing the development of targeted therapeutic strategies.
methodsWe employed spatial transcriptomics to map Tgfb1 mRNA expression in murine jawbone tissues, focusing on its distribution in the periodontium. Pseudotime analysis was performed to assess expression patterns and infer temporal dynamics. Human PDLSCs were used as a model to investigate the effects of TGF-β1 signaling, with assays conducted to examine DNA methylation, senescence phenotypes, cell cycle arrest, and underlying signaling pathways.
resultsSpatial transcriptomic profiling revealed enriched Tgfb1 expression in the periodontium, with upregulation tendencies. In human PDLSCs, TGF-β1 treatment induced a senescent phenotype marked by G2 phase cell cycle arrest and increased reactive oxygen species (ROS) accumulation. Mechanistically, TGF-β1 triggered ROS production through DNA methylation-mediated silencing of PRKAG2, a gene encoding AMPKγ2, resulting in ROS accumulation, DNA damage, and ATM signaling activation. Importantly, inhibition of ROS with N-acetyl-l-cysteine (NAC) or reversal of PRKAG2 epigenetic silencing with decitabine mitigated PDLSC senescence by suppressing ATM signaling.
conclusionOur work presents the first spatially resolved transcriptomic landscape of murine jawbone tissues and uncovers DNA methylation as a crucial mechanism underlying TGF-β1-induced PDLSC senescence. These findings illuminate a previously unrecognized link between TGF-β1 signaling, ROS production, and epigenetic regulation, offering promising avenues for developing stem cell-based therapies to attenuate age-related periodontal diseases and improve systemic health.
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