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Blood, 1 October 2004, Vol. 104, No. 7, pp. 2060-2064. Prepublished online as a Blood First Edition Paper on June 1, 2004; DOI 10.1182/blood-2003-12-4231. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-12-4231v1 104/7/2060    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hakobyan, N. Articles by Valentino, L. A. Search for Related Content PubMed PubMed Citation Articles by Hakobyan, N. Articles by Valentino, L. A. Related Collections Hemostasis, Thrombosis, and Vascular Biology Red Cells Oncogenes and Tumor Suppressors Gene Expression Related Article in Blood Online Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Pathobiology of hemophilic synovitis I: overexpression of mdm2 oncogene Narine Hakobyan, Tamara Kazarian, Adnan A. Jabbar, Kausar J. Jabbar, and Leonard A. Valentino From the Departments of Pediatrics and Immunology/Microbiology, Rush Children's Hospital and Rush University, Chicago, IL. Hemophilia is a genetic disease caused by a deficiency of blood coagulation factor VIII or IX. Bleeding into joints is the most frequent manifestation of hemophilia. Hemarthrosis results in an inflammatory and proliferative disorder termed hemophilic synovitis (HS). In time, a debilitating, crippling arthritis, hemophilic arthropathy, develops. Although the clinical sequence of events from joint bleeding to synovitis to arthropathy is well documented, the component or components in blood and the molecular changes responsible for hemophilic synovitis are not known. Iron has long been suspected to be the culprit but direct evidence has been lacking. Previously, we showed that iron increased human synovial cell proliferation and induced c-myc expression. Here we show that bleeding into a joint in vivo and iron in vitro result in increased expression of the p53-binding protein, mdm2. Iron induced the expression of mdm2 by normal human synovial cells approximately 8-fold. In a murine model of human hemophilia A, hemarthrosis resulted in pathologic changes observed in human hemophilic synovitis and a marked increase in synovial cell proliferation. Iron, in vitro, induced the expression of mdm2. The molecular changes induced by iron in the blood may be the basis of the increase in cell proliferation and the development of hemophilic synovitis. (Blood. 2004;104:2060-2064) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Are oncogenes responsible for hemophilic arthropathy? Thomas Abshire Blood 2004 104: 1911-1912. [Full Text] [PDF] Related Letter in Blood Online: HFE mutations in the pathobiology of hemophilic arthropathy Eugenia Cruz, Graça Porto, Sara Morais, Manuel Campos, and Maria de Sousa Blood 2005 105: 3381-3382. [Full Text] [PDF] This article has been cited by other articles: R. McClain, N. Hakobyan, and L. A. Valentino Vascularization of the Synovial Membrane in Hemophilic Synovitis. Blood (ASH Annual Meeting Abstracts), November 16, 2006; 108(11): 4018 - 4018. [Abstract] [Full Text] [PDF] M. Hoffman, A. Harger, A. Lenkowski, U. Hedner, H. R. Roberts, and D. M. Monroe Cutaneous wound healing is impaired in hemophilia B Blood, November 1, 2006; 108(9): 3053 - 3060. [Abstract] [Full Text] [PDF] E. Cruz, G. Porto, S. Morais, M. Campos, and M. de Sousa HFE mutations in the pathobiology of hemophilic arthropathy Blood, April 15, 2005; 105(8): 3381 - 3382. [Full Text] [PDF]

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