ArticleJournal of tissue engineering and regenerative medicine2018
Metformin induces osteoblastic differentiation of human induced pluripotent stem cell-derived mesenchymal stem cells.
Article in Journal of tissue engineering and regenerative medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 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.
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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
55 citing papers in PubMed, 108 citations in OpenAlex.
- Metformin as a Metabolic Reprogramming Interface in Host-Pathogen and Bone Microenvironment Crosstalk: A Dual-Target Strategy Against Antimicrobial Resistance and Osteoporotic Bone Loss.Antibiotics (Basel, Switzerland) · 2026Review
- From diabetes to dentistry: metformin targets mitochondrial-immune crosstalk to restore periodontal homeostasis.Journal of translational medicine · 2026Review
- From Diabetes to Degenerative Diseases: The Multifaceted Action of Metformin.International journal of molecular sciences · 2025Review
- Combination of Periodontal Ligament Stem Cells and Metformin via Organic Cation Transporters for Periodontal Regeneration in Rats.Biomolecules · 2025Article
- Effect of Octacalcium Phosphate on Osteogenic Differentiation of Induced Pluripotent Stem Cells in a 3D Hybrid Spheroid Culture.Biomimetics (Basel, Switzerland) · 2025Article
- Metformin and bone metabolism: unraveling their direct and indirect effects.Therapeutic advances in endocrinology and metabolism · 2025Review
- Novel Fast-Setting and Mechanically-Strong Calcium Phosphate Pulp-Capping Cement with Metformin Release to Enhance Dental Pulp Stem Cells.Bioengineering (Basel, Switzerland) · 2024Article
- Moldable Alginate/Hydroxyapatite Hydrogel Loaded with Metformin Enhanced Regeneration of the Rabbit Mandibular Defects.Journal of maxillofacial and oral surgery · 2024Article
- Improvement of osteogenic differentiation potential of placenta-derived mesenchymal stem cells by metformin via AMPK pathway activation.Stem cell research & therapy · 2024Article
- Effect of Applying 1% Metformin on Guided Bone Regeneration Processes with Bovine-Derived Xenografts.Journal of clinical medicine · 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
- Applications of Metformin in Dentistry-A review.Journal of Taibah University Medical Sciences · 2023Review
- Recent progress in bone-repair strategies in diabetic conditions.Materials today. Bio · 2023Review
- Small-Molecule Loaded Biomimetic Biphasic Scaffold for Osteochondral Regeneration: An In Vitro and In Vivo Study.Bioengineering (Basel, Switzerland) · 2023Article
- Metformin increases bone marrow adipose tissue by promoting mesenchymal stromal cells apoptosis.Aging · 2023Article
- Impact of Metformin on Periodontal and Peri-Implant Soft and Hard Tissue.International journal of environmental research and public health · 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
- Metformin can mitigate skeletal dysplasia caused by Pck2 deficiency.International journal of oral science · 2022Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Metformin, a first-line antidiabetic drug used by millions of patients, has been shown to have potential osteogenic properties. The present study was performed to test the hypothesis that clinically relevant doses of metformin promote the osteogenic differentiation and mineralization of induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs). iPSC-MSCs were treated with metformin (10 μm) to assess cell viability, osteogenic differentiation, mineralization and activation of the LKB1/AMP-activated protein kinase (AMPK) signalling pathway, a surrogate marker of metformin action. To determine its potential application in MSC-based bone and periodontal tissue engineering, iPSC-MSCs were also treated with metformin when seeded on to calcium phosphate cement (CPC) scaffolds. Immunoblotting and cellular uptake assays showed that iPSC-MSCs express functional organic cation transporter-1 (OCT-1), a transmembrane protein that mediates the intracellular uptake of metformin. Although metformin treatment did not impair iPSC-MSC viability, it significantly stimulated alkaline phosphatase activity, enhanced mineralized nodule formation and increased expression of osteogenic markers, including Runt-related transcription factor 2 (RUNX2) and osterix. Inhibition of LKB1 activity, a common upstream AMPK kinase, markedly reversed metformin-induced AMPK activation, RUNX2 expression and nuclear localization. Moreover, metformin substantially increased mineralized nodule formation of iPSC-MSC seeded on CPC scaffolds. Collectively, functional OCT-expressing iPSC-MSCs responded to metformin by inducing an osteogenic effect in part mediated by the LKB1/AMPK pathway. Considering the widespread use of metformin in diabetics, this work may lead to novel tissue-engineering platforms where autogenous OCT-expressing iPSC-MSCs might be used to enhance bone and periodontal regeneration in diabetic patients prescribed with daily doses of metformin.
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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.