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Publication
Fibrinolysis is essential for fracture repair and prevention of heterotopic
ossification.
Authors Yuasa M, Mignemi NA, Nyman JS, Duvall CL, Schwartz HS, Okawa A, Yoshii T,
Bhattacharjee G, Zhao C, Bible JE, Obremskey WT, Flick MJ, Degen JL, Barnett JV,
Cates JM, Schoenecker JG
Submitted By Jonathan Schoenecker on 8/4/2017
Status Published
Journal The Journal of clinical investigation
Year 2015
Date Published 8/3/2015
Volume : Pages 125 : 3117 - 31
PubMed Reference 26214526
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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