Experimental haemophilic synovitis: rationale and development of a murine model of human factor VIII deficiency.
Haemophilia is a genetic disease as a result of the deficiency of blood coagulation factor VIII or IX. Bleeding is common, especially into joints where an inflammatory, proliferative synovitis develops resulting in a debilitating arthritis, haemophilic arthropathy. The pathogenesis of blood-induced haemophilic synovitis (HS) is poorly understood. The gross, microscopic and ultrastructural changes that occur in the synovial membrane following human and experimental hemarthrosis have been described. Repeated episodes of bleeding induce synoviocyte hypertrophy and hyperplasia, an intense neovascular response and inflammation of the synovial membrane. The component(s) in blood that initiates these changes is(are) not known, although iron is often proposed as one possibility. Here, we describe a novel murine model of human haemophilia A, which facilitates the examination of large number of animals and tissue specimens. The effects of hemarthrosis on the physical, gross and microscopic changes evoked following joint bleeding are described. Controlled, blunt trauma to the knee joint consistently resulted in joint swelling because of a combination of bleeding and inflammation. Hemosiderin was found in the synovial membrane. Similar to hemarthrosis in human haemophilia, joint bleeding resulted in acute morbidity evidenced by inactivity, weight loss and immobility. With time the animals recovered. The model of experimental murine HS described here has utility in the study of the pathogenesis of HS. This is the first of a series of articles, which will discuss the pathophysiology and characterize the model, with comparison of his model to others which have been published previously. It should provide a useful model to test potential therapeutic interventions.
Valentino
L A
LA
Departments of Pediatrics and Immunology/Microbiology, Rush Children's Hospital and Rush University, Chicago, IL 60612, USA. lvalentino@rush.edu
Hakobyan
N
N
Kazarian
T
T
Jabbar
K J
KJ
Jabbar
A A
AA
D000818:Animals; D015992:Body Mass Index; D006395:Hemarthrosis / Q000209:etiology* / Q000473:pathology; D006467:Hemophilia A / Q000150:complications* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D009043:Motor Activity; D013585:Synovitis / Q000209:etiology* / Q000473:pathology; D015431:Weight Loss; D014949:Wounds, Nonpenetrating / Q000150:complications / Q000473:pathology