ArticleJournal of endodontics2018
Metformin Enhances the Differentiation of Dental Pulp Cells into Odontoblasts by Activating AMPK Signaling.
Article in Journal of endodontics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Combination of metformin and double antibiotic paste for the regeneration of non-vital immature teeth: a preliminary randomized clinical study.BMC oral health · 2023Trial
- Novel Metformin-Containing Antibacterial Composite for Root Caries Restorations.Materials (Basel, Switzerland) · 2026Article
- Effects of anti-diabetic medications on the teeth, oral soft and hard tissues, saliva, and implants: a scoping review.BDJ open · 2026Review
- Dose-dependent effects of Metformin on proliferation and odontogenic differentiation of dental pulp stem cells.BMC oral health · 2026Article
- Novel Metformin-Encapsulating Poly(lactic-co-glycolic acid) Microspheres in Calcium Phosphate Pulp-Capping Cement with Dental Pulp Stem Cells for Regenerative Applications.Materials (Basel, Switzerland) · 2026Article
- Serum Starvation Regulates Autophagy of Human Periodontal Ligament Cells Through Reactive Oxygen Species Mediated Adenosine Monophosphate-Activated Protein Kinase/Mechanistic Target of RAPAMYCIN Axis.International dental journal · 2025Article
- Combination of Periodontal Ligament Stem Cells and Metformin via Organic Cation Transporters for Periodontal Regeneration in Rats.Biomolecules · 2025Article
- Novel Fast-Setting and Mechanically-Strong Calcium Phosphate Pulp-Capping Cement with Metformin Release to Enhance Dental Pulp Stem Cells.Bioengineering (Basel, Switzerland) · 2024Article
- Improvement of osteogenic differentiation potential of placenta-derived mesenchymal stem cells by metformin via AMPK pathway activation.Stem cell research & therapy · 2024Article
- Synergistic effect of metformin and vitamin DRegenerative therapy · 2024Article
- Metformin-mediated effects on mesenchymal stem cells and mechanisms: proliferation, differentiation and aging.Frontiers in pharmacology · 2024Review
- Walnut Kernel Oil and Defatted Extracts Enhance Mesenchymal Stem Cell Stemness and Delay Senescence.Molecules (Basel, Switzerland) · 2023Article
- The Role of Cellular Metabolism in Maintaining the Function of the Dentine-Pulp Complex: A Narrative Review.Metabolites · 2023Review
- Application of Dental Pulp Stem Cells for Bone and Neural Tissue Regeneration in Oral and Maxillofacial Region.Stem cells international · 2023Review
- Degradable hydrogel fibers encapsulate and deliver metformin and periodontal ligament stem cells for dental and periodontal regeneration.Journal of applied oral science : revista FOB · 2023Article
- Effects of Metformin Delivery via Biomaterials on Bone and Dental Tissue Engineering.International journal of molecular sciences · 2022Review
- The role of AMPK-dependent pathways in cellular and molecular mechanisms of metformin: a new perspective for treatment and prevention of diseases.Inflammopharmacology · 2022Review
- Metformin carbon nanodots promote odontoblastic differentiation of dental pulp stem cells by pathway of autophagy.Frontiers in bioengineering and biotechnology · 2022Article
- Therapeutic potential of stem cells from human exfoliated deciduous teeth infusion into patients with type 2 diabetes depends on basal lipid levels and islet function.Stem cells translational medicine · 2021Article
- Effect of Ascorbic Acid on Differentiation, Secretome and Stemness of Stem Cells from Human Exfoliated Deciduous Tooth (SHEDs).Journal of personalized medicine · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
introductionMetformin is a first-line drug for treating type 2 diabetes that regulates the differentiation of mesenchymal stem cells. Its effects on human dental pulp cells (DPCs) remain unknown. This study aimed to investigate the effects of metformin on the proliferation and differentiation of DPCs.
methodsA live/dead viability assay kit was used to examine the effects of metformin on the cell viability of DPCs. Cell proliferation was analyzed using a cell counting kit (CCK-8; Dojindo, Tokyo, Japan). Levels of phosphorylated and unphosphorylated adenosine 5'-monophosphate-activated protein kinase (AMPK) were quantified by Western blot analysis in response to metformin and the AMPK signaling inhibitor Compound C (EMD Chemicals, San Diego, CA). The effects of Compound C on the metformin-induced odontoblast differentiation of DPCs were determined by alkaline phosphatase activity assay and von Kossa staining, and the expression of odontoblastic markers was evaluated by reverse-transcription polymerase chain reaction analysis.
resultsDPCs exhibited mesenchymal stem cell characteristics using flow cytometry. Different doses of metformin were shown to be cytocompatible with DPCs, yielding >90% cell viability. None of the concentrations of metformin up to 50 μmol/L affected cell proliferation. The Western blot assay showed that DPCs express functional organic cation transporter 1, a transmembrane protein that mediates the intracellular uptake of metformin. Metformin significantly activated the AMPK pathway in a dose-dependent manner. In addition, it stimulated alkaline phosphatase activity; enhanced mineralized nodule formation; and increased the expression of odontoblastic markers including dentin sialophosphoprotein, dentin matrix protein 1, runt-related transcription factor 2, and osteocalcin. Moreover, pretreatment with Compound C, a specific AMPK inhibitor, markedly reversed metformin-induced odontoblastic differentiation and cell mineralization.
conclusionsThis study shows that metformin can induce DPC differentiation and mineralization in an AMPK-dependent manner and that this well-tolerated antidiabetic drug has potential in regenerative endodontics as well as in other regenerative applications.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.