Metformin reverses impaired osteogenesis due to hyperglycemia-induced neutrophil extracellular traps formation
Abstract
Diabetic patients suffer from delayed fracture healing and impaired osteogenic function, but the underlying pathophysiological mechanisms are not fully understood. Neutrophil extracellular traps (NETs) formed by neutrophils in high glucose microenvironments affect the healing of wounds and other tissues. Some evidence supports that NETs may inhibit osteogenic processes in the microenvironment through sustained inflammatory activation. In this study, we observed that high glucose-induced NETs led to sustained inflammatory activation of macrophages. Pro-inflammatory NETs inhibited the osteogenic function of osteoblasts in vitro. A bone defect healing model based on diabetic rat animal models confirmed that bone healing was impaired in a high glucose environment, but this process could be reversed by DNase I, a NETs clearance agent. More importantly, the classic hypoglycemic drug metformin had a similar antagonistic effect as DNase I and could reverse the inhibitory effect of NETs on osteogenesis in a high-glucose environment. In summary, we found that NETs formation induced by high glucose microenvironment is a potential cause of osteogenic dysfunction in diabetic patients, and metformin can reverse this osteogenic disadvantage.
Read the paper
Related studies
- Metformin as an adjuvant in breast cancer treatment
- Metformin Lysosomal Targeting: A Novel Aspect to Be Investigated for Metformin Repurposing in Neurodegenerative Diseases?
- Aberrant HSF1 signaling activation underlies metformin amelioration of myocardial infarction in mice
- Metformin induces ZFP36 by mTORC1 inhibition in cervical cancer-derived cell lines
- Protein Interaction Network for Identifying Vascular Response of Metformin (Oral Antidiabetic)
- Preventing Long COVID With Metformin
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.