Experimental haemophilic arthropathy in a mouse model of a massive haemarthrosis: gross, radiological and histological changes.
Recurrent haemarthrosis results in chronic synovitis and destructive arthropathy. The long-term effect of a single haemorrhage is not known. To investigate the histopathological changes following a single, but major joint haemorrhage, an animal model of massive haemarthrosis without mechanical trauma was developed and is described in this manuscript. The knee joint capsule of mice deficient in coagulation factor VIII or IX and non-haemophilic wild type mice was punctured to induce a one time, but massive haemorrhage. The single joint puncture resulted in acute haemarthrosis in both types of haemophilic mice but not in wild type mice. Subsequent to injury, the changes in the knee joints were analysed using gross, histological and radiographic assessments and compared with the uninjured knee. In addition, a novel imaging modality, micro-computed tomography, was used to document the structural damage to the joint. Our results indicate that the long-term changes classically observed in patients with advanced haemophilic arthropathy are evident following a single massive haemarthrosis. This model will allow a thorough investigation of the pathobiology of blood-induced joint disease and will be useful to test the efficacy of innovative therapeutic strategies to prevent haemophilic synovitis and arthropathy.
Hakobyan
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N
The RUSH Hemophilia and Thrombophilia Center, and Department of Pediatrics, Rush University Medical Center, 1653 West Congress Parkway, Chicago, IL 60612, USA. narine_hakobyan@rush.edu
Enockson
C
C
Cole
A A
AA
Sumner
D R
DR
Valentino
L A
LA
D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism; D004195:Disease Models, Animal; D005169:Factor VIII / Q000627:therapeutic use; D006395:Hemarthrosis / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D006467:Hemophilia A / Q000150:complications* / Q000188:drug therapy; D051379:Mice; D018345:Mice, Knockout; D011509:Proteoglycans / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D013585:Synovitis / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D055114:X-Ray Microtomography / Q000379:methods
D011509:Proteoglycans; D011994:Recombinant Proteins; D005169:Factor VIII