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Prepublished online as a Blood First Edition Paper on December 27, 2002; DOI 10.1182/blood-2002-09-2839. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-09-2839v1 101/8/2983    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 Chagraoui, H. Articles by Wendling, F. Search for Related Content PubMed PubMed Citation Articles by Chagraoui, H. Articles by Wendling, F. Related Collections Hematopoiesis and Stem Cells Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 April 2003, Vol. 101, No. 8, pp. 2983-2989 HEMATOPOIESIS Stimulation of osteoprotegerin production is responsible for osteosclerosis in mice overexpressing TPO Hédia Chagraoui, Micheline Tulliez, Tarek Smayra, Emiko Komura, Stéphane Giraudier, Theodore Yun, Nathalie Lassau, William Vainchenker, and Françoise Wendling From the IFR 54-INSERM U 362, Institut Gustave Roussy, Villejuif, France; Service d'Anatomie et Cytologie Pathologiques, Hôpital Cochin, Paris, France; LIPA, IFR 54, Institut Gustave Roussy, Villejuif, France; and Department of Immunology, University of Washington, Seattle. Myelofibrosis and osteosclerosis are prominent features arising in mice overexpressing thrombopoietin (TPO). The pivotal role of transforming growth factor 1 (TGF-1) in the pathogenesis of myelofibrosis has been documented, but the mechanisms mediating osteosclerosis remain unclear. Here, we used mice deficient in osteoprotegerin (OPG), a secreted inhibitor of bone resorption, to determine whether osteosclerosis occurs through a deregulation of osteoclastogenesis. Marrow cells from opg-deficient mice (opg/) or wild-type (WT) littermates were infected with a retrovirus encoding TPO and engrafted into an opg/ or WT background for long-term reconstitution. The 4 combinations of graft/host (WT/WT, opg//opg/, opg//WT, and WT/opg/) were studied. Elevation of TPO and TGF-1 levels in plasma was similar in the 4 experimental groups and all the mice developed a similar myeloproliferative syndrome associated with severe myelofibrosis. Osteosclerosis developed in WT hosts engrafted with WT or opg/ hematopoietic cells and was associated with increased OPG levels in plasma and decreased osteoclastogenesis. In contrast, opg/ hosts exhibited an osteoporotic phenotype and a growth of bone trabeculae was rarely seen. These findings suggest that osteosclerosis in mice with TPO overexpression occurs predominantly via an up-regulation of OPG in host stromal cells leading to disruption of osteoclastogenesis. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J.-J. Lataillade, O. Pierre-Louis, H. C. Hasselbalch, G. Uzan, C. Jasmin, M.-C. Martyre, M.-C. Le Bousse-Kerdiles, and on behalf of the French INSERM and the European EU Does primary myelofibrosis involve a defective stem cell niche? From concept to evidence Blood, October 15, 2008; 112(8): 3026 - 3035. [Abstract] [Full Text] [PDF] R. 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