ArticlePloS one2020
Impact of hyperglycemia and treatment with metformin on ligature-induced bone loss, bone repair and expression of bone metabolism transcription factors.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- Leiurus quinquestratus venom promotes β islets regeneration and restores glucose level in streptozotocin induced type 2 diabetes mellitus in rats.Scientific reports · 2025Article
- Metformin and bone metabolism: unraveling their direct and indirect effects.Therapeutic advances in endocrinology and metabolism · 2025Review
- Impact of Metformin on Periodontal and Peri-Implant Soft and Hard Tissue.International journal of environmental research and public health · 2023Review
- Advancing our understanding of the influence of drug induced changes in the gut microbiome on bone health.Frontiers in endocrinology · 2023Review
- Osteoporosis and Alveolar Bone Health in Periodontitis Niche: A Predisposing Factors-Centered Review.Cells · 2022Review
- The Potential Therapeutic Role of Metformin in Diabetic and Non-Diabetic Bone Impairment.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Article
- Pathogenesis and treatment of wound healing in patients with diabetes after tooth extraction.Frontiers in endocrinology · 2022Review
- Effect of Aging on Homeostasis in the Soft Tissue of the Periodontium: A Narrative Review.Journal of personalized medicine · 2021Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study evaluated the influence of type 2 diabetes mellitus on bone loss, bone repair and cytokine production in hyperglycemic rats, treated or not with metformin. The animals were distributed as follow: Non-Hyperglycemic (NH), Non Hyperglycemic with Ligature (NH-L), Treated Non Hyperglycemic (TNH), Treated Non Hyperglycemic with Ligature Treated (TNH-L), Hyperglycemic (H), Treated Hyperglycemic (TH), Hyperglycemic with Ligature (H-L), Treated Hyperglycemic with Ligature (TH-L). At 40th day after induction of hyperglycemia, the groups NH-L, TNH-L, H-L, TH-L received a ligature to induce periodontitis. On the 69th, the TNH, TNH-L, TH, TH-L groups received metformin until the end of the study. Bone repair was evaluated at histometric and the expression levels of Sox9, RunX2 and Osterix. Analysis of the ex-vivo expression of TNF-α, IFN-γ, IL-12, IL-4, TGF-β, IL-10, IL-6 and IL-17 were also evaluated. Metformin partially reverse induced bone loss in NH and H animals. Lower OPG/RANKL, increased OCN and TRAP expression were observed in hyperglycemic animals, and treatment with metformin partially reversed hyperglycemia on the OPG/RANKL, OPN and TRAP expression in the periodontitis. The expression of SOX9 and RunX2 were also decreased by hyperglycemia and metformin treatment. Increased ex vivo levels of TNF-α, IL-6, IL-4, IL-10 and IL-17 was observed. Hyperglycemia promoted increased IL-10 levels compared to non-hyperglycemic ones. Treatment of NH with metformin was able to mediate increased levels of TNF-α, IL-10 and IL-17, whereas for H an increase of TNF-α and IL-17 was detected in the 24- or 48-hour after stimulation with LPS. Ligature was able to induce increased levels of TNF-α and IL-17 in both NH and H. This study revealed the negative impact of hyperglycemia and/or treatment with metformin in the bone repair via inhibition of transcription factors associated with osteoblastic differentiation.
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