ArticleBone2018
Temporary inhibition of the plasminogen activator inhibits periosteal chondrogenesis and promotes periosteal osteogenesis during appendicular bone fracture healing.
Article in Bone, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Effects of aminocaproic acid on perioperative hidden blood loss in elderly patients with femoral intertrochanteric fracture treated with proximal femoral nail anti-rotation.The Journal of international medical research · 2019Trial
- Potential Targeting Mechanisms for Bone-Directed Therapies.International journal of molecular sciences · 2024Review
- Periosteum Containing Implicit Stem Cells: A Progressive Source of Inspiration for Bone Tissue Regeneration.International journal of molecular sciences · 2024Review
- Insight into the function of tetranectin in human diseases: A review and prospects for tetranectin-targeted disease treatment.Heliyon · 2024Review
- Efficacy and safety of using aminocaproic acid and tranexamic acid during the perioperative period for treating trochanteric fractures in elderly femurs.BMC musculoskeletal disorders · 2023Article
- Periosteal Skeletal Stem and Progenitor Cells in Bone Regeneration.Current osteoporosis reports · 2022Review
- Progress of Periosteal Osteogenesis: The Prospect of In Vivo Bioreactor.Orthopaedic surgery · 2022Review
- Osteogenic and Chondrogenic Potential of Periosteum-Derived Mesenchymal Stromal Cells: Do They Hold the Key to the Future?Pharmaceuticals (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
introductionAminocaproic acid is approved as an anti-fibrinolytic for use in joint replacement and spinal fusion surgeries to limit perioperative blood loss. Previous animal studies have demonstrated a pro-osteogenic effect of aminocaproic acid in spine fusion models. Here, we tested if aminocaproic acid enhances appendicular bone healing and we sought to uncover the effect of aminocaproic acid on osteoprogenitor cells (OPCs) during bone regeneration.
methodsWe employed a well-established murine femur fracture model in adult C57BL/6J mice after receiving two peri-operative injections of aminocaproic acid. Routine histological assays, biomechanical testing and micro-CT analyses were utilized to assess callus volume, and strength, progenitor cell proliferation, differentiation, and remodeling in vivo. Two disparate ectopic transplantation models were used to study the effect of the growth factor milieu within the early fracture hematoma on osteoprogenitor cell fate decisions.
resultsAminocaproic acid treated femur fractures healed with a significantly smaller cartilaginous callus, and this effect was also observed in the ectopic transplantation assays. We hypothesized that aminocaproic acid treatment resulted in a stabilization of the early fracture hematoma, leading to a change in the growth factor milieu created by the early hematoma. Gene and protein expression analysis confirmed that aminocaproic acid treatment resulted in an increase in Wnt and BMP signaling and a decrease in TGF-β-signaling, resulting in a shift from chondrogenic to osteogenic differentiation in this model of endochondral bone formation.
conclusionThese experiments demonstrate for the first time that inhibition of the plasminogen activator during fracture healing using aminocaproic acid leads to a change in cell fate decision of periosteal osteoprogenitor cells, with a predominance of osteogenic differentiation, resulting in a larger and stronger bony callus. These findings may offer a promising new use of aminocaproic acid, which is already FDA-approved and offers a very safe risk profile.
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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.