ArticleDiabetologia2015
Diabetes reduces mesenchymal stem cells in fracture healing through a TNFα-mediated mechanism.
Article in Diabetologia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 124 citations in OpenAlex.
- Effect of aging on healing of mandibular tooth extraction socket in a rat model.European journal of oral sciences · 2026Article
- Role of the immune microenvironment in bone regeneration and progress in immune-modulating bone nanobiomaterials.Journal of Zhejiang University. Science. B · 2026Review
- Harnessing MSC Immunomodulation in Orthopedics: Clinical Insights for Comorbidities.Stem cell reviews and reports · 2026Review
- Article
- Biomaterial regulation of excessive inflammation restores osteoimmune homeostasis in diabetic bone regeneration.Regenerative biomaterials · 2026Review
- FTO-mediated m6A modification regulates the osteogenic differentiation of ADSCs by targeting FOXO1.Stem cell research & therapy · 2025Article
- Hydroxylated fullerene promotes fracture healing in ovariectomized combined type 2 diabetic mice.Journal of orthopaedic surgery and research · 2025Article
- The role and mechanism of mesenchymal stem cells in immunomodulation of type 1 diabetes mellitus and its complications: recent research progress and challenges: a review.Stem cell research & therapy · 2025Review
- A novel strategy for bone defect repair: Stromal cell-derived factor 1α sustained-release acellular fish scale scaffolds combined with injection of bone marrow mesenchymal stem cells promote bone regeneration.Materials today. Bio · 2025Article
- Harnessing Mesenchymal Stromal Cells for Advanced Wound Healing: A Comprehensive Review of Mechanisms and Applications.International journal of molecular sciences · 2024Review
- GPC3-mediated metabolic rewiring of diabetic mesenchymal stromal cells enhances their cardioprotective functions via PKM2 activation.iScience · 2024Article
- Recent Advances in Hydrogel Technology in Delivering Mesenchymal Stem Cell for Osteoarthritis Therapy.Biomolecules · 2024Review
- High glucose microenvironment and human mesenchymal stem cell behavior.World journal of stem cells · 2024Article
- The treatment efficacy of bone tissue engineering strategy for repairing segmental bone defects under diabetic condition.Frontiers in bioengineering and biotechnology · 2024Article
- Inhibition of PTEN promotes osteointegration of titanium implants in type 2 diabetes by enhancing anti-inflammation and osteogenic capacity of adipose-derived stem cells.Frontiers in bioengineering and biotechnology · 2024Article
- Advantages and Limitations of Diabetic Bone Healing in Mouse Models: A Narrative Review.Biomedicines · 2023Review
- Recent progress in bone-repair strategies in diabetic conditions.Materials today. Bio · 2023Review
- Hippo-YAP/TAZ signaling in osteogenesis and macrophage polarization: Therapeutic implications in bone defect repair.Genes & diseases · 2023Review
- Diabetes impairs fracture healing through Foxo1 mediated disruption of ciliogenesis.Cell death discovery · 2023Article
- Expression of proinflammatory cytokines and proinsulin by bone marrow-derived cells for fracture healing in long-term diabetic mice.BMC musculoskeletal disorders · 2023Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
aims/hypothesisDiabetes interferes with bone formation and impairs fracture healing, an important complication in humans and animal models. The aim of this study was to examine the impact of diabetes on mesenchymal stem cells (MSCs) during fracture repair.
methodsFracture of the long bones was induced in a streptozotocin-induced type 1 diabetic mouse model with or without insulin or a specific TNFα inhibitor, pegsunercept. MSCs were detected with cluster designation-271 (also known as p75 neurotrophin receptor) or stem cell antigen-1 (Sca-1) antibodies in areas of new endochondral bone formation in the calluses. MSC apoptosis was measured by TUNEL assay and proliferation was measured by Ki67 antibody. In vitro apoptosis and proliferation were examined in C3H10T1/2 and human-bone-marrow-derived MSCs following transfection with FOXO1 small interfering (si)RNA.
resultsDiabetes significantly increased TNFα levels and reduced MSC numbers in new bone area. MSC numbers were restored to normal levels with insulin or pegsunercept treatment. Inhibition of TNFα significantly reduced MSC loss by increasing MSC proliferation and decreasing MSC apoptosis in diabetic animals, but had no effect on MSCs in normoglycaemic animals. In vitro experiments established that TNFα alone was sufficient to induce apoptosis and inhibit proliferation of MSCs. Furthermore, silencing forkhead box protein O1 (FOXO1) prevented TNFα-induced MSC apoptosis and reduced proliferation by regulating apoptotic and cell cycle genes. CONCLUSIONS/
interpretationDiabetes-enhanced TNFα significantly reduced MSC numbers in new bone areas during fracture healing. Mechanistically, diabetes-enhanced TNFα reduced MSC proliferation and increased MSC apoptosis. Reducing the activity of TNFα in vivo may help to preserve endogenous MSCs and maximise regenerative potential in diabetic patients.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.