ArticleThe Journal of clinical investigation2015
Fibrinolysis is essential for fracture repair and prevention of heterotopic ossification.
Article in The Journal of clinical investigation, 2015. 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 49 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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 98 citations in OpenAlex.
- Biomaterial-mediated blood clot formation: a key to unlocking osteogenic synergy for bone regeneration.Bone research · 2026Review
- Fibrin, from blood to bone: a review.Bone reports · 2026Review
- Early Biological Orchestration in Fracture Healing: Decoding the Crosstalk between Inflammation, Coagulation, and Metabolism.Stem cell reviews and reports · 2026Review
- Role of the immune microenvironment in bone regeneration and progress in immune-modulating bone nanobiomaterials.Journal of Zhejiang University. Science. B · 2026Review
- Biomaterial regulation of excessive inflammation restores osteoimmune homeostasis in diabetic bone regeneration.Regenerative biomaterials · 2026Review
- How to explain the beneficial effects of platelet-rich plasma.Periodontology 2000 · 2025Review
- Lymphatic platelet thrombosis limits bone repair by precluding lymphatic transporting DAMPs.Nature communications · 2025Article
- Denervation‑induced NRG3 aggravates muscle heterotopic ossification via the ErbB4/PI3K/Akt signaling pathway.Molecular medicine reports · 2025Article
- Hypoxia-Mimicking Mediated Macrophage-Elimination of Erythrocytes Promotes Bone Regeneration via Regulating Integrin αAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- RNA therapeutics to control fibrinolysis: review on applications in biology and medicine.Journal of thrombosis and haemostasis : JTH · 2024Review
- The emerging role of tranexamic acid and its principal target, plasminogen, in skeletal health.Acta pharmaceutica Sinica. B · 2024Review
- Human versus Rat PRF on Collagen Membranes: A Pilot Study of Mineralization in Rat Calvaria Defect Model.Bioengineering (Basel, Switzerland) · 2024Article
- Implications of siRNA Therapy in Bone Health: Silencing Communicates.Biomedicines · 2024Review
- Maintaining the balance: the critical role of plasmin activity in orthopedic surgery injury response.Journal of thrombosis and haemostasis : JTH · 2023Review
- Bioceramics/Electrospun Polymeric Nanofibrous and Carbon Nanofibrous Scaffolds for Bone Tissue Engineering Applications.Materials (Basel, Switzerland) · 2023Review
- The role of Meteorin-like in skeletal development and bone fracture healing.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2022Article
- Osteocyte-specific dentin matrix protein 1 : the role of mineralization regulation in low-magnitude high-frequency vibration enhanced osteoporotic fracture healing.Bone & joint research · 2022Article
- Variable Response to Antifibrinolytics Correlates with Blood-loss and Transfusion in Posterior Spinal Fusion.Spine deformity · 2022Article
- Determining the pharmacologic window of bisphosphonates that mitigates severe injury-induced osteoporosis and muscle calcification, while preserving fracture repair.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Bone formation during fracture repair inevitably initiates within or around extravascular deposits of a fibrin-rich matrix. In addition to a central role in hemostasis, fibrin is thought to enhance bone repair by supporting inflammatory and mesenchymal progenitor egress into the zone of injury. However, given that a failure of efficient fibrin clearance can impede normal wound repair, the precise contribution of fibrin to bone fracture repair, whether supportive or detrimental, is unknown. Here, we employed mice with genetically and pharmacologically imposed deficits in the fibrin precursor fibrinogen and fibrin-degrading plasminogen to explore the hypothesis that fibrin is vital to the initiation of fracture repair, but impaired fibrin clearance results in derangements in bone fracture repair. In contrast to our hypothesis, fibrin was entirely dispensable for long-bone fracture repair, as healing fractures in fibrinogen-deficient mice were indistinguishable from those in control animals. However, failure to clear fibrin from the fracture site in plasminogen-deficient mice severely impaired fracture vascularization, precluded bone union, and resulted in robust heterotopic ossification. Pharmacological fibrinogen depletion in plasminogen-deficient animals restored a normal pattern of fracture repair and substantially limited heterotopic ossification. Fibrin is therefore not essential for fracture repair, but inefficient fibrinolysis decreases endochondral angiogenesis and ossification, thereby inhibiting fracture repair.
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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.