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Blood, 15 April 2006, Vol. 107, No. 8, pp. 3098-3105. Prepublished online as a Blood First Edition Paper on December 22, 2005; DOI 10.1182/blood-2005-08-3450. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: 2005-08-3450v1 107/8/3098    most recent Alert me when this article is cited Alert me if a correction is posted 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 Anderson, G. Articles by Lentzsch, S. Search for Related Content PubMed PubMed Citation Articles by Anderson, G. Articles by Lentzsch, S. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 26, 2005 Accepted November 30, 2005 Thalidomide derivative CC-4047 inhibits osteoclast formation by down regulation of PU.1 Gulsum Anderson, Margarete Gries, Noriyoshi Kurihara, Tadashi Honjo, Judy Anderson, Vera Donnenberg, Albert Donnenberg, Irene Ghobrial, Markus Y Mapara, David Stirling, David Roodman, and Suzanne Lentzsch* Division of Hematology/Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA Department of Hematology, Oncology and Tumorimmunology, University Medical Center Charite, Robert-Rossle-Klinik, Humboldt University, Berlin, Germany Celgene Corporation, Warren, NJ, USA * Corresponding author; email: lentzschs{at}upmc.edu. CC-4047 (Actimid®), an immunomodulatory analog of thalidomide, inhibits multiple myeloma with unknown effects on the human osteoclast lineage. Early osteoclast progenitors are of hematopoietic origin and differentiate into mature bone resorbing multinucleated osteoclasts. We investigated effects of CC-4047 and thalidomide on human osteoclastogenesis, using in vitro receptor activator of NF-B ligand/macrophage colony-stimulating factor stimulated bone marrow cell cultures. Treating bone marrow cultures with CC-4047 for three weeks decreased osteoclast formation accompanied by complete inhibition of bone resorption. The inhibitory effect was similar when cultures were treated for three weeks or only for the first week (90% inhibition), indicating that CC-4047 inhibits early stages of osteoclast formation. Inhibition of osteoclastogenesis by CC-4047 was mediated by a shift of lineage commitment to granulocyte colony-forming units at the expense of granulocyte-macrophage colony-forming units. Further studies revealed that this shift in lineage commitment was mediated through down-regulation of PU.1. Treatment with thalidomide resulted in significantly less potent inhibition of osteoclast formation and bone resorption. These results provide evidence that CC-4047 blocks osteoclast differentiation during early phases of osteoclastogenesis. Therefore, CC-4047 might be a valuable drug for targeting both tumors and osteoclastic activity in patients with multiple myeloma and other diseases associated with osteolytic lesions. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: W. Aerbajinai, J. Zhu, Z. Gao, K. Chin, and G. P. Rodgers Thalidomide induces {gamma}-globin gene expression through increased reactive oxygen species mediated p38 MAPK signaling and histone H4 acetylation in adult erythropoiesis Blood, October 15, 2007; 110(8): 2864 - 2871. [Abstract] [Full Text] [PDF]

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