ArticleStem cell research & therapy2022
Metformin combats high glucose-induced damage to the osteogenic differentiation of human periodontal ligament stem cells via inhibition of the NPR3-mediated MAPK pathway.
Article in Stem cell research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Novel Metformin-Containing Antibacterial Composite for Root Caries Restorations.Materials (Basel, Switzerland) · 2026Article
- 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
- Dose-dependent effects of Metformin on proliferation and odontogenic differentiation of dental pulp stem cells.BMC oral health · 2026Article
- Efficacy of metformin as an adjunct in periodontitis: A systematic analysis.Journal of Taibah University Medical Sciences · 2026Review
- Article
- Diabetes and periodontitis: the role of a high-glucose microenvironment in periodontal tissue cells and corresponding therapeutic strategies.Stem cell research & therapy · 2025Review
- Metformin-Enhanced Secretome from Periodontal Ligament Stem Cells Promotes Functional Recovery in an Inflamed Periodontal Model: In Vitro Study.Journal of functional biomaterials · 2025Article
- [Ginsenoside Rb3 regulates the phosphorrylated extracellular signal-regulated kinase signaling pathway to alleviate inflammatory responses and promote osteogenesis in rats with periodontitis].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2025Article
- Pyroptotic macrophages induce disruption of glutamate metabolism in periodontal ligament stem cells contributing to their compromised osteogenic potential.Cell proliferation · 2024Article
- Metformin-mediated effects on mesenchymal stem cells and mechanisms: proliferation, differentiation and aging.Frontiers in pharmacology · 2024Review
- Exploratory Research for HIF-1α Overexpression Tumor Antigen in the Activation of Dendritic Cells and the Potent Anti-Tumor Immune Response.Cancer management and research · 2024Article
- Applications of Metformin in Dentistry-A review.Journal of Taibah University Medical Sciences · 2023Review
- Advances in combined application of dental stem cells and small-molecule drugs in regenerative medicine.Human cell · 2023Review
- Long non-coding RNA AC018926.2 regulates palmitic acid exposure-compromised osteogenic potential of periodontal ligament stem cells via the ITGA2/FAK/AKT pathway.Cell proliferation · 2023Article
- Resistin targets TAZ to promote osteogenic differentiation through PI3K/AKT/mTOR pathway.iScience · 2023Article
- Overview of the main biological mechanisms linked to changes in periodontal ligament stem cells and the inflammatory microenvironment.Journal of Zhejiang University. Science. B · 2023Review
- NADPH-dependent ROS accumulation contributes to the impaired osteogenic differentiation of periodontal ligament stem cells under high glucose conditions.Frontiers in endocrinology · 2023Article
- Recent advances on small molecules in osteogenic differentiation of stem cells and the underlying signaling pathways.Stem cell research & therapy · 2022Review
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Authors and funding
10 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundHigh glucose-induced damage to the osteogenic differentiation of human periodontal ligament stem cells (PDLSCs) has long been a challenge to periodontal regeneration for diabetic individuals. Metformin is an anti-hyperglycemic drug that exhibits abundant biological activities associated with cell metabolism and downstream tissue regeneration. However, how metformin combats damage to PDLSC osteogenic differentiation under high glucose and the underlying mechanisms remain unknown.
methodsOsteogenic differentiation of PDLSCs was assessed by alkaline phosphatase (ALP) staining, ALP activity, Alizarin Red staining and quantitative assay, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. RNA-seq analysis was performed to screen target genes of metformin, and the effects of target genes were confirmed using lentivirus transfection. Western blot analysis was also used to detect the protein level of underlying signaling pathways.
resultsWe found that osteogenic differentiation of PDLSCs under high glucose was decreased, and metformin addition enhanced this capacity of differentiation. Furthermore, the results of RNA-seq analysis showed that natriuretic peptide receptor 3 (NPR3) was upregulated in PDLSCs under high glucose and downregulated after metformin addition. When the underlying pathways involved were investigated, we found that upregulation of NPR3 can compromise the metformin-enhanced PDLSC osteogenic differentiation and activate the MAPK pathway (especially the p38 MAPK and Erk1/2 pathway), and that inhibition of the NPR3-mediated p38 MAPK or Erk1/2 pathway enhanced the osteogenic differentiation of PDLSCs under high glucose.
conclusionsThe present study suggests that metformin may enhance the osteogenic differentiation of PDLSCs under high glucose via downregulation of NPR3 and inhibition of its downstream MAPK pathway. This is the first report identifying the involvement of NPR3-mediated MAPK pathway in the metformin-enhanced osteogenic differentiation, indicating that NPR3 antagonists, such as metformin, may be feasible therapeutics for periodontal tissue regeneration in diabetic individuals.
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