title: Physiopathology of haemophilic arthropathy.
abstract: Haemophilic arthropathy, which shares some clinical and biological injury characteristics with rheumatoid arthritis, is characterized by two main features: chronic proliferative synovitis and cartilage destruction. It is the consequence of repeated extravasation of blood into joint cavities, but its exact pathogenesis, particularly with regard to early changes in the joint, is still incompletely understood. This review presents recent findings obtained in experiments performed in vitro and using animal models, which have improved our knowledge of the pathogenesis of haemophilic arthropathy. These experimental studies show that haemophilic arthropathy is a multifactorial event in which the deposit of iron in the joints appears to exert a central role. First, iron may promote the apoptosis of chondrocytes by catalysing the formation of oxygen metabolites; this may explain the fact that intra-articular blood exerts a directly harmful effect on cartilage before, and independent of synovial changes. Secondly, iron may also act on the synovial membrane by favouring its proliferation through the induction of proto-oncogenes involved in cellular proliferation and stimulation of inflammatory cytokines as well as abrogation of apoptosis. These two processes, one degenerative and cartilage-mediated, the other inflammatory and synovium-mediated could occur in parallel or sequentially. Overall, it may be expected that these experimental results will yield new therapeutic strategies capable of effectively preventing the occurrence of this still serious and common complication in patients with severe haemophilia.
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. F.Lafeber@umcutrecht.nl
authors.forename: F P J G
authors.initials: FP
authors.lastname: Lafeber
authors.forename: P
authors.initials: P
authors.lastname: Miossec
authors.forename: L A
authors.initials: LA
authors.lastname: Valentino
mesh_terms: D000818:Animals; D002357:Cartilage Diseases / Q000378:metabolism / Q000503:physiopathology*; D002358:Cartilage, Articular / Q000378:metabolism / Q000503:physiopathology; D006395:Hemarthrosis / Q000378:metabolism / Q000503:physiopathology*; D006467:Hemophilia A / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007501:Iron / Q000378:metabolism; D023421:Models, Animal; D013583:Synovial Membrane / Q000378:metabolism / Q000503:physiopathology; D013585:Synovitis / Q000378:metabolism / Q000503:physiopathology*; D046509:Tissue Culture Techniques
chemical_list: D007501:Iron