ArticlePloS one2014
Delayed fracture healing and increased callus adiposity in a C57BL/6J murine model of obesity-associated type 2 diabetes mellitus.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 117 citations in OpenAlex.
- Bone‑origin repair in diabetic foot ulcers: Mechanisms of callus formation and endocrine effects in healing (Review).International journal of molecular medicine · 2026Review
- IL-1β/EPAS1-Associated Ferroptotic Stress Impairs Skeletal Stem/Progenitor Cell Function in Inflammation-Associated Fracture Nonunion.Current issues in molecular biology · 2026Article
- Article
- Intermittent fasting alleviates obesity-associated impairments in bone fracture healing: Exploring the role of gut microbiome.Bone reports · 2025Article
- High-fat diet, intestinal microecology and bone loss.Nutrition & metabolism · 2025Review
- NLRP3 inflammasome impairs fracture repair in Rheumatoid arthritis through RhoA/Rac1-IL1β axis-mediated suppression of osteoblast differentiation.Journal of orthopaedic translation · 2025Article
- Novel perspectives on leptin in osteoarthritis: Focus on aging.Genes & diseases · 2024Review
- Single-cell RNA sequencing reveals a distinct profile of bone immune microenvironment and decreased osteoclast differentiation in type 2 diabetic mice.Genes & diseases · 2024Article
- Hdac3 deficiency limits periosteal reaction associated with Western diet feeding in female mice.Journal of cellular and molecular medicine · 2024Article
- Article
- Advantages and Limitations of Diabetic Bone Healing in Mouse Models: A Narrative Review.Biomedicines · 2023Review
- Cannabidiol and Cannabigerol, Nonpsychotropic Cannabinoids, as Analgesics that Effectively Manage Bone Fracture Pain and Promote Healing in Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Article
- M2 macrophage-derived exosomes promote diabetic fracture healing by acting as an immunomodulator.Bioactive materials · 2023Article
- The role of PIEZO ion channels in the musculoskeletal system.American journal of physiology. Cell physiology · 2023Review
- Adipokines at the crossroads of obesity and mesenchymal stem cell therapy.Experimental & molecular medicine · 2023Review
- Parathyroid hormone therapy improves MRSA-infected fracture healing in a murine diabetic model.Frontiers in cellular and infection microbiology · 2023Article
- Distinct defects in early innate and late adaptive immune responses typify impaired fracture healing in diet-induced obesity.Frontiers in immunology · 2023Article
- Molecular signatures distinguish senescent cells from inflammatory cells in aged mouse callus stromal cells.Frontiers in endocrinology · 2023Article
- Assessment of Bone Fracture Healing Using Micro-Computed Tomography.Journal of visualized experiments : JoVE · 2022Article
- Contrasting effects ofeLife · 2022Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
introductionImpaired healing and non-union of skeletal fractures is a major public health problem, with morbidity exacerbated in patients with diabetes mellitus (DM). DM is prevalent worldwide and affects approximately 25.8 million US adults, with >90% having obesity-related type 2 DM (T2DM). While fracture healing in type 1 DM (T1DM) has been studied using animal models, an investigation into delayed healing in an animal model of T2DM has not yet been performed.
methodsMale C57BL/6J mice at 5 weeks of age were placed on either a control lean diet or an experimental high-fat diet (HFD) for 12 weeks. A mid-diaphyseal open tibia fracture was induced at 17 weeks of age and a spinal needle was used for intra-medullary fixation. Mice were sacrificed at days 7, 10, 14, 21, 28, and 35 for micro-computed tomography (μCT), histology-based histomorphometry and molecular analyses, and biomechanical testing.
resultsHFD-fed mice displayed increased body weight and impaired glucose tolerance, both characteristic of T2DM. Compared to control mice, HFD-fed mice with tibia fractures showed significantly (p<0.001) decreased woven bone at day 28 by histomorphometry and significantly (p<0.01) decreased callus bone volume at day 21 by μCT. Interestingly, fracture calluses contained markedly increased adiposity in HFD-fed mice at days 21, 28, and 35. HFD-fed mice also showed increased PPARγ immunohistochemical staining at day 14. Finally, calluses from HFD-fed mice at day 35 showed significantly (p<0.01) reduced torsional rigidity compared to controls. DISCUSSION: Our murine model of T2DM demonstrated delayed fracture healing and weakened biomechanical properties, and was distinctly characterized by increased callus adiposity. This suggests altered mesenchymal stem cell fate determination with a shift to the adipocyte lineage at the expense of the osteoblast lineage. The up-regulation of PPARγ in fracture calluses of HFD-fed mice is likely involved in the proposed fate switching.
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