Essentials Validating the F8 rat as a new intermediate-size animal model of hemophilic
arthropathy.
Factor VIII (FVIII) treated F8(-/-) rats suffered induced
hemarthrosis analyzed by histopathology. F8 (-/-) animals develop hemophilic
arthropathy upon
hemarthrosis, preventable by FVIII treatment. The F8 (-/-) rat presents as a new pharmacologic model of hemophilic
arthropathy.
SUMMARY: Background Translational animal models of
hemophilia are valuable for determining the pathobiology of the disease and its co-morbidities (e.g. hemophilic
arthropathy, HA). The
biologic mechanisms behind the development of HA, a painful and debilitating condition, are not completely understood. We recently characterized a F8(-/-) rat, which could be a new preclinical model of HA. Objectives To establish the F8(-/-) rat as a model of HA by determining if the F8(-/-) rat develops HA resembling human HA after an induced joint bleed and whether a second joint bleed causes further
disease progression. Methods Wild-type and F8(-/-) rats were treated with vehicle or recombinant human
factor VIII (rhFVIII) prior to a needle-induced joint bleed. Joint swelling was measured prior to injury, the following 7 days and upon
euthanasia. Histologic sections of the joint were stained, and athropathic changes identified and scored with regard to
synovitis, bone remodelling, cartilage degradation and
hemosiderin deposition. Results Vehicle-treated F8(-/-) rats experienced marked joint swelling and developed chronic degenerative joint changes (i.e.
fibrosis of the subsynovial membrane, chondrocyte loss and excessive bone remodeling). Treatment with rhFVIII reduced or prevented swelling and degenerative joint changes, returning the F8(-/-) animals to a wild-type phenotype. Conclusion The hemophilic phenotype of the F8(-/-) rat resulted in a persistent
hemarthrosis following an induced joint bleed. This caused development of HA resembling human HA, which was prevented by rhFVIII treatment, confirming the potential of the F8(-/-) rat as a model of HA.