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Blood, 15 August 2005, Vol. 106, No. 4, pp. 1407-1414. Prepublished online as a Blood First Edition Paper on May 5, 2005; DOI 10.1182/blood-2005-03-1080. This Article Full Text (PDF) All Versions of this Article: 2005-03-1080v1 106/4/1407    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 Ehrlich, L. A Articles by Giuliani, N. Search for Related Content PubMed PubMed Citation Articles by Ehrlich, L. A Articles by Giuliani, N. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 16, 2005 Accepted April 22, 2005 IL-3 is a potential inhibitor of osteoblast differentiation in multiple myeloma Lori A Ehrlich, Ho Yeon Chung, Irene Ghobrial, Sun Jin Choi, Francesca Morandi, Simona Colla, Vittorio Rizzoli, David Roodman*, and Nicola Giuliani Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA Cattedra di Ematologia, Universita Degli Studi di Parma, Parma, Italy Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; VA-Pittsburgh Medical Center, Pittsburgh, PA, USA * Corresponding author; email: roodmangd{at}upmc.edu. Bone destruction in multiple myeloma is characterized both by markedly increased osteoclastic bone destruction and severely impaired osteoblast activity. We reported that IL-3 levels are increased in bone marrow plasma of myeloma patients compared to normals and that IL-3 stimulates osteoclast formation. However, the effects of IL-3 on osteoblasts are unknown. Therefore, to determine if IL-3 inhibits osteoblast growth and differentiation, we treated primary mouse and human marrow stromal cells with IL-3 and assessed osteoblast differentiation. IL-3 inhibited basal and BMP-2 stimulated osteoblast formation in a dose-dependent manner, without affecting cell growth. Importantly, marrow plasma from patients with high IL-3 levels inhibited osteoblast differentiation which could be blocked by anti-IL-3. However, IL-3 did not inhibit osteoblast differentiation of osteoblast-like cell lines. In contrast, IL-3 increased the number of CD45+ hematopoietic cells in stromal cell cultures. Depletion of the CD45+ cells abolished the inhibitory effects of IL-3 on osteoblasts, and reconstitution of the cultures with CD45+ cells restored the capacity of IL-3 to inhibit osteoblast differentiation. These data suggest that IL-3 plays a dual role in the bone destructive process in myeloma by both stimulating osteoclast and indirectly inhibiting osteoblast formation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Kukreja, S. Radfar, B.-H. Sun, K. Insogna, and M. V. Dhodapkar Dominant role of CD47-thrombospondin-1 interactions in myeloma-induced fusion of human dendritic cells: implications for bone disease Blood, October 15, 2009; 114(16): 3413 - 3421. [Abstract] [Full Text] [PDF] E. Terpos, O. Sezer, P. I. Croucher, R. Garcia-Sanz, M. Boccadoro, J. San Miguel, J. Ashcroft, J. Blade, M. Cavo, M. Delforge, et al. The use of bisphosphonates in multiple myeloma: recommendations of an expert panel on behalf of the European Myeloma Network Ann. Onc., August 1, 2009; 20(8): 1303 - 1317. [Abstract] [Full Text] [PDF] O. 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