ArticleJournal of orthopaedic translation2023
Metformin attenuates diabetes-induced osteopenia in rats is associated with down-regulation of the RAGE-JAK2-STAT1 signal axis.
Article in Journal of orthopaedic translation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Cellular signaling crosstalk between osteoporosis and diabetes: Common mechanisms and therapeutic targets (Review).Biomedical reports · 2026Review
- JAK-STAT signaling: molecular mechanism and targeted treatment in dento-maxillofacial abnormalities.International journal of oral science · 2026Review
- Discovery and identification of semaphorin 4D as a bioindicator of high fracture incidence in type 2 diabetic mice with glucose control.Journal of advanced research · 2026Article
- Lactate-functionalized 3D-printed PCL/nHA scaffold drives BMSC osteogenesis via metabolic-epigenetic crosstalk.Materials today. Bio · 2025Article
- Targeting the AGEs-RAGE axis: pathogenic mechanisms and therapeutic interventions in diabetic wound healing.Frontiers in medicine · 2025Review
- Metformin and bone metabolism: unraveling their direct and indirect effects.Therapeutic advances in endocrinology and metabolism · 2025Review
- Localized delivery of metformin via 3D printed GelMA-Nanoclay hydrogel scaffold for enhanced treatment of diabetic bone defects.Journal of orthopaedic translation · 2024Article
- Pharmacology and therapeutic potential of agarwood and agarwood tree leaves in periodontitis.Frontiers in pharmacology · 2024Review
- Qianggu concentrate: unlocking bone protection power via antioxidative SIRT1/NRF2/HO-1 pathways in type 2 diabetic osteoporosis.Frontiers in pharmacology · 2024Article
- Trabecular Bone Score (TBS) in Individuals with Type 2 Diabetes Mellitus: An Updated Review.Journal of clinical medicine · 2023Review
- Innovation and Translation of Biological and Biomaterial Treatment for Challenging Musculoskeletal Disorders.Journal of orthopaedic translation · 2023Article
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Osteopenia and fragile fractures are diabetes-associated complications. Many hypoglycemic drugs have effects on bone metabolism. Metformin, as is a prescribed medication for type 2 diabetes mellitus (T2DM), had been reported to have osteoprotective effects beyond its hypoglycemic effect, however the potential mechanism behind these effects remains unclear. In this study, we aimed to investigate the comprehensive effects of metformin on bone metabolism in T2DM rat model and elucidate the potential mechanism. Methods: Goto-Kakizaki spontaneous T2DM rats with significant hyperglycemia were treated with/without metformin for 20 weeks. Glucose tolerance was tested and all rats were weighed every two weeks. The osteoprotective effects of metformin in diabetic rats were determined by quantifying serum bone biomarkers, μ-CT imaging, histological staining, bone histomorphometry, and biomechanical properties analyses. Potential targets of metformin in the treatment of T2DM and osteoporosis were predicted using network pharmacology. The effects of metformin on mesenchymal stem cells (C3H10) cultured in high glucose medium were evaluated by CCK-8 assay, alkaline phosphatase (ALP) staining, qPCR and western blotting. Results: This study demonstrated that metformin significantly attenuated osteopenia, decreased serum glucose and glycated serum protein (GSP) levels, improved bone microarchitecture, and biomechanical properties in GK rats with T2DM. Metformin significantly increased biomarkers of bone formation, and significantly decreased muscle ubiquitin C (Ubc) expression. Network pharmacology analysis found that signal transducer and activator of transcription1 (STAT1) would be a potential target of metformin for regulating bone metabolism. Metformin increased C3H10 cell viability Conclusions: Our results demonstrate that metformin attenuated osteopenia and improved bone microarchitecture in GK rats with T2DM and significantly promoted stem cell osteogenic differentiation under high glucose condition. The effects of metformin on bone metabolism are closely associated with the suppression of RAGE-JAK2-STAT1 signaling axis. The translational potential of this article: Our research provides experiment evidence and potential mechanistic rationale for the use of metformin as an effective candidate for diabetes-induced osteopenia treatment.
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