ArticleEMBO molecular medicine2015
Low-dose TNF augments fracture healing in normal and osteoporotic bone by up-regulating the innate immune response.
Article in EMBO molecular medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
What it found
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
67 citing papers in PubMed, 117 citations in OpenAlex.
- Neutrophils: The Overlooked Regenerative Role in Bone Repair.Stem cell reviews and reports · 2026Review
- Skeletal stem and progenitor cell niche organization, regulation and repair.Reviews in endocrine & metabolic disorders · 2026Review
- Biologic immunomodulators and spinal fusion: evidence, mechanisms, and perioperative considerations.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026Review
- Recent progress in immunomodulation-based strategies for bone repair.Regenerative therapy · 2026Review
- The Osteoimmunologic Basis of Biologic and Bioengineered Scaffolds in Fracture Healing.Bioengineering (Basel, Switzerland) · 2026Review
- Smart biomaterials for skeletal aging repair and regeneration.Bone research · 2026Review
- The roles of the nerve-immune axis in modulating bone regeneration.Bone research · 2026Review
- Urolithin A supplementation alleviates osteogenic disfunction and promotes bone fracture healing in inflammatory environments.Food & nutrition research · 2026Article
- Real-world pharmacovigilance of drug-induced osteoporosis: a focus on antiretroviral therapy and toxicological mechanisms in the elderly.Frontiers in pharmacology · 2026Article
- Biomaterial regulation of excessive inflammation restores osteoimmune homeostasis in diabetic bone regeneration.Regenerative biomaterials · 2026Review
- Mechanical force-induced oncostatin M secretion by Jun-positive neutrophils promotes craniofacial bone regeneration for midface hypoplasia treatment.Stem cell research & therapy · 2025Article
- Article
- CCL2/CCR2 Signalling in Mesenchymal Stem/Progenitor Cell Recruitment and Fracture Healing in Mice.Journal of cellular and molecular medicine · 2024Article
- Trained innate immunity modulates osteoblast and osteoclast differentiation.Stem cell reviews and reports · 2024Article
- The local and systemic effects of immune function on fracture healing.OTA international : the open access journal of orthopaedic trauma · 2024Review
- Deletion of CD47 from Schwann cells and macrophages hastens myelin disruption/dismantling and scavenging in Schwann cells and augments myelin debris phagocytosis in macrophages.Journal of neuroinflammation · 2023Article
- An in vivo study to investigate an original intramedullary bone graft harvesting technology.European journal of medical research · 2023Article
- Biomaterial scaffolds regulate macrophage activity to accelerate bone regeneration.Frontiers in bioengineering and biotechnology · 2023Review
- Systemic and local inflammatory response after implantation of biomaterial in critical bone injuries.Acta cirurgica brasileira · 2023Article
- Neutrophils delay repair process in Wallerian degeneration by releasing NETs outside the parenchyma.Life science alliance · 2022Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
The mechanism by which trauma initiates healing remains unclear. Precise understanding of these events may define interventions for accelerating healing that could be translated to the clinical arena. We previously reported that addition of low-dose recombinant human TNF (rhTNF) at the fracture site augmented fracture repair in a murine tibial fracture model. Here, we show that local rhTNF treatment is only effective when administered within 24 h of injury, when neutrophils are the major inflammatory cell infiltrate. Systemic administration of anti-TNF impaired fracture healing. Addition of rhTNF enhanced neutrophil recruitment and promoted recruitment of monocytes through CCL2 production. Conversely, depletion of neutrophils or inhibition of the chemokine receptor CCR2 resulted in significantly impaired fracture healing. Fragility, or osteoporotic, fractures represent a major medical problem as they are associated with permanent disability and premature death. Using a murine model of fragility fractures, we found that local rhTNF treatment improved fracture healing during the early phase of repair. If translated clinically, this promotion of fracture healing would reduce the morbidity and mortality associated with delayed patient mobilization.
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Registered trials
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.