ArticleStem cell research & therapy2025
BMDMs in metabolic memory impair fracture healing in diabetes.
Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.
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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.
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Who cites it
2 citing papers in PubMed.
- Mechanical Intelligence in Bone Regeneration: Bridging Material and Cellular Memory for Enhanced Healing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Correction: BMDMs in metabolic memory impair fracture healing in diabetes.Stem cell research & therapy · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors.
Funding
Abstract
backgroundThe risk of fractures nonunion and delayed union in diabetes mellitus remains elevated despite glucose-lowering therapies. We hypothesized that bone marrow-derived macrophages (BMDMs) can be induced in the status of metabolic memory and still impair fracture healing when hyperglycemia stimulus disappears.
methodsDiabetic mice were divided into control (Ctrl), diabetic (DM), and diabetic with glucose control (DM/GC) groups. Fracture healing was assessed by micro-CT and histology, evaluating callus volume, bone volume/total volume (BV/TV), and inflammatory markers. In vitro, bone marrow-derived macrophages (BMDMs) were exposed to high glucose (HG) for varying periods to simulate hyperglycemia-induced metabolic memory, followed by normalization. Pro-inflammatory cytokines and macrophage polarization (M1/M2) were assessed via ELISA and flow cytometry. Osteogenesis and angiogenesis were evaluated in co-culture assays. RNA-seq and ATAC-seq were performed to analyze gene expression and chromatin accessibility, focusing on inflammatory pathways and CEBPB.
resultsAll data show that BMDMs play a significant role in the sustained effects of hyperglycemia on fracture healing even after glucose normalization in diabetic animals. Hyperglycemia-induced metabolic memory in BMDMs resulted in increased pro-inflammatory cytokines and a higher proportion of M1 macrophages, which impaired osteogenesis and angiogenesis. The co-culture medium from BMDMs in metabolic memory conditions suppressed osteogenesis in BMSCs and angiogenesis in HUVECs. Integrated analysis of RNA-seq and ATAC-seq in BMDMs revealed that inflammatory pathways were upregulated, with CEBPB identified as a key factor. Silencing CEBPB reversed these adverse effects and enhanced fracture healing in a diabetic model.
conclusionsOur results demonstrate the reason why the glucose-lowering therapies is unsuccessful in reducing the risk of fractures nonunion and delayed union in patients with diabetes mellitus, and shed light on a new strategy for the disease.
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