ArticleScientific reports2024
Metformin enhances osteogenic differentiation of BMSC by modulating macrophage M2 polarization.
Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Bibliometric analysis of metformin as an immunomodulator (2013-2024).Frontiers in immunology · 2024Pooled it
- Review
- Metformin as an Innate Immune Modulator: Metabolic and Epigenetic Reprogramming of Innate Immune Cells and Therapeutic Implications.Current issues in molecular biology · 2026Review
- The Impact of Large-Scale Expansion on the Functional Properties of Mesenchymal Stem Cells.Stem cell reviews and reports · 2026Review
- CD169Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Bone marrow cellular profile in patients with diabetes: association of statin therapy with CD34+ cells.Frontiers in endocrinology · 2026Observational
- Targeting innate immunity to modulate bone metabolism: a novel strategy for osteoporosis treatment.Frontiers in aging · 2026Review
- Mechanisms and Drug-Augmenting Strategies of Mesenchymal Stem Cells for Preserving β-Cell in Type 2 Diabetes.Drug design, development and therapy · 2026Review
- Sirtuin 3 promotes osteogenic differentiation of bone marrow mesenchymal stem cells by regulating macrophage polarization under high glucose.Scientific reports · 2025Article
- Trolox, r-irisin and resveratrol cocktail to counteract osteoblast metabolism alterations in osteoarthritis and osteoporosis.Journal of bone and mineral metabolism · 2025Article
- Metformin carbon dots-based osteogenic and protein delivery system to promote bone regeneration in periodontitis.Bioactive materials · 2025Article
- Ionizing radiation-mediated dendritic cell maturation exacerbates inflammatory response of bone marrow mesenchymal stem cells and impairs osteogenesis in radiation-induced jaw injury.Stem cell research & therapy · 2025Article
- Article
- Overexpression of interleukin-4 using adeno-associated virus is a potential strategy to enhance bone regeneration.JBMR plus · 2025Article
- Modic changes: From potential molecular mechanisms to future research directions (Review).Molecular medicine reports · 2025Review
- Multi-omics analysis of synovial tissue and fluid reveals differentially expressed proteins and metabolites in osteoarthritis.Journal of translational medicine · 2025Article
- Metformin and bone metabolism: unraveling their direct and indirect effects.Therapeutic advances in endocrinology and metabolism · 2025Review
- Efferocytosis-induced metabolic shift in bone macrophages drives lactate production and modulates inflammation and osteoclastogenesis.Frontiers in immunology · 2025Article
- Osteogenic effects of metformin and exenatide on bone regeneration in non-diabetic rats: A Micro-CT and histological study.Journal of oral and maxillofacial pathology : JOMFPArticle
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Authors and funding
7 authors.
Funding
Abstract
Bone marrow-derived mesenchymal stem cells (BMSCs) are capable of developing into osteoblastic cell lines in vitro and regenerating bone tissue in vivo, and they are considered to be a reliable source for bone regenerative medicine. In recent years, studies have shown that the immune microenvironment is important for osteogenesis, in which macrophages are an important component of innate immunity and coordinate with stem cells. Metformin (Met), a hypoglycemic drug that exerts a powerful effect on metabolic signaling, has been shown to modulate inflammatory responses and osteogenic activity. However, whether metformin modulates macrophage polarization and subsequently affects osteogenesis remains to be elucidated. In the present study, we investigated the potential immunomodulatory capacity of metformin on macrophage inflammatory responses and phenotypic switching, and the subsequent effects on osteogenic differentiation of BMSCs. Flow cytometry and qPCR were used to study the effects of metformin on macrophage phenotypic regulation. qPCR, ALP, ARS and calcium content measurement and ALP activity assay were used to determine the effects of macrophage-secreted activators on the osteogenic differentiation of BMSCs. Our study demonstrates that metformin can improve the immune microenvironment by modulating macrophage polarization towards an anti-inflammatory phenotype, promoting an increase in a range of anti-inflammatory factors and inhibiting pro-inflammatory factors. This was characterized by increased expression of IL-10 and CD206, Arg-1 and decreased expression of IL-1β, TNF-α, IL-6 and iNOS. In addition, metformin-modulated macrophage-conditioned medium promoted osteogenic differentiation of BMSCs, increased the expression levels of genes (ALP, Runx-2, OCN, and Col-1), enhanced ALP activity, and significantly formed mineralized nodules. In conclusion, our new study elucidates that metformin can promote osteogenic differentiation of BMSCs by modulating macrophage phenotype and thereby.
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