ArticleStem cells international2022
Metformin Facilitates Osteoblastic Differentiation and M2 Macrophage Polarization by PI3K/AKT/mTOR Pathway in Human Umbilical Cord Mesenchymal Stem Cells.
Article in Stem cells international, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Association of metformin use with fracture risk in type 2 diabetes: A systematic review and meta-analysis of observational studies.Frontiers in endocrinology · 2022 · on this mapPooled it
- Unveiling the role of circulating monocyte-macrophage polarization state and PD-L1/PD-L2 expression in newly diagnosed pediatric ITP.Blood research · 2026Article
- Metformin as an Innate Immune Modulator: Metabolic and Epigenetic Reprogramming of Innate Immune Cells and Therapeutic Implications.Current issues in molecular biology · 2026Review
- The role of metformin in extracellular matrix-based three-dimensional cell culture Models: A mini-review on therapeutic potentials.Biochemistry and biophysics reports · 2026Review
- Regulation of calcium delivery and pore structure via osteoinductive microspheres of HA/CS/PGCL for orbital bone regeneration.Regenerative biomaterials · 2026Article
- In Vivo Investigation of Osteogenesis and Angiogenesis of Modified Polycaprolactone-Hydroxyapatite-Zinc Oxide Electrospun Nanofibers Loaded with Metformin.Annals of biomedical engineering · 2025Article
- Research Progress on Natural Products That Regulate miRNAs in the Treatment of Osteosarcoma.Biology · 2025Review
- The potential crosstalk genes and molecular mechanisms between systemic lupus erythematosus and periodontitis.Frontiers in genetics · 2025Article
- Metformin and bone metabolism: unraveling their direct and indirect effects.Therapeutic advances in endocrinology and metabolism · 2025Review
- Osteoporosis in Adrenal Insufficiency: Could Metformin be Protective?Indian journal of clinical biochemistry : IJCB · 2025Review
- Multiomics Analysis of Molecules Associated with Cancer in Mesenchymal-Stem-Cell-(MSC)-Derived Exosome-Treated Hepatocellular Carcinoma Cells.Current issues in molecular biology · 2024Article
- Improvement of osteogenic differentiation potential of placenta-derived mesenchymal stem cells by metformin via AMPK pathway activation.Stem cell research & therapy · 2024Article
- Metformin enhances osteogenic differentiation of BMSC by modulating macrophage M2 polarization.Scientific reports · 2024Article
- mTOR Dysregulation, Insulin Resistance, and Hypertension.Biomedicines · 2024Review
- Metformin prevents the onset and progression of intervertebral disc degeneration: New insights and potential mechanisms (Review).International journal of molecular medicine · 2024Review
- Umbilical cord mesenchymal stem cells: A novel approach to intervention of ovarian ageing.Regenerative therapy · 2024Review
- Metformin-mediated effects on mesenchymal stem cells and mechanisms: proliferation, differentiation and aging.Frontiers in pharmacology · 2024Review
- The Differential Effect of Metformin on Osteocytes, Osteoblasts, and Osteoclasts.Current osteoporosis reports · 2023Review
- Advances in the study of macrophage polarization in inflammatory immune skin diseases.Journal of inflammation (London, England) · 2023Review
- Sensor Array-Enabled Identification of Drugs for Repolarization of Macrophages to Anti-Inflammatory Phenotypes.Analytical chemistry · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mesenchymal stem cells (MSCs) are the most promising multipotent stem cells that can differentiate into osteoblasts, chondrocytes, and adipocytes. This cellular flexibility contributes to widespread clinical use of MSCs in tissue repair and regeneration. The immune system is a key player in regulating bone remodeling. In recent years, the association between the immune system and bone metabolism has become an increasing focus of interest. Metformin, a glucose-lowering drug, exerts powerful impact on metabolic signaling. However, whether metformin can modulate bone metabolism or whether metformin can influence immune milieu by regulation of macrophages has not been thoroughly elucidated. Herein, we specifically explored the complex interactions between macrophages and human umbilical cord mesenchymal stem cells (UC-MSCs) in the context of metformin. Our research demonstrated that metformin not only stimulated osteogenesis of UC-MSCs but also influenced the immune system via promoting M2 but reducing M1 macrophages. Mechanically, we found that metformin-treated M2 macrophages possessed more potent osteoinductive capacity in our coculture system. Molecularly, these metformin-stimulated M2 macrophages facilitated osteogenesis via activating the PI3K/AKT/mTOR pathway. As demonstrated by using PI3K-specific inhibitor LY294002, we found that the pathway inhibitor partly reversed osteoinductive activity which was activated by coculture of metformin-treated M2 macrophages. Overall, our novel research illuminated the cooperative and synergistic effects of metformin and M2 macrophages on the dynamic balance of bone metabolism.
Identifiers
What OpenQuestion holds
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.