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Blood, 1 October 2005, Vol. 106, No. 7, pp. 2472-2483. Prepublished online as a Blood First Edition Paper on June 2, 2005; DOI 10.1182/blood-2004-12-4986. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-12-4986v1 106/7/2472    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 Giuliani, N. Articles by Rizzoli, V. Search for Related Content PubMed PubMed Citation Articles by Giuliani, N. Articles by Rizzoli, V. Related Collections Neoplasia Cell Adhesion and Motility Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Myeloma cells block RUNX2/CBFA1 activity in human bone marrow osteoblast progenitors and inhibit osteoblast formation and differentiation Nicola Giuliani, Simona Colla, Francesca Morandi, Mirca Lazzaretti, Roberto Sala, Sabrina Bonomini, Maria Grano, Silvia Colucci, Mirija Svaldi, and Vittorio Rizzoli From the Laboratory of Hematology, the Hematology and Bone Marrow Transplantation (BMT) Center, the Department of Internal Medicine and Biomedical Science, the Department of Pathology, and the Department of Experimental Medicine, University of Parma, Parma, Italy; the Department of Human Anatomy and Histology, University of Bari, Italy; and Ematologia, Bolzano (Bozen), Italy. Decreased bone formation contributes to the development of bone lesions in multiple myeloma (MM) patients. In this study, we have investigated the effects of myeloma cells on osteoblast formation and differentiation and the potential role of the critical osteoblast transcription factor RUNX2/CBFA1 (Runt-related transcription factor 2/core-binding factor Runt domain subunit 1) in the inhibition of osteoblastogenesis in MM. We found that human myeloma cells suppress the formation of human osteoblast progenitors in bone marrow (BM) cultures. Moreover, an inhibitory effect on osteocalcin, alkaline phosphatase, collagen I mRNA, protein expression, and RUNX2/CBFA1 activity by human preosteoblastic cells was observed in cocultures with myeloma cells. The inhibitory effect was more pronounced in the cell-to-cell contact conditions compared with those without the contact and involved the very late antigen 4 (VLA-4) integrin system. Among the soluble osteoblast inhibitors screened, we show the potential contribution of interleukin-7 (IL-7) in the inhibitory effect on osteoblast formation and RUNX2/CBFA1 activity by human myeloma cells in coculture. Finally, our in vitro results were supported in vivo by the finding of a significant reduction in the number of Runx2/Cbfa1-positive cells in the BM biopsies of patients with MM who had osteolytic lesions compared with those who did not have bone lesions, suggesting the critical involvement of RUNX2/CBFA1 in the decreased bone formation in MM. (Blood. 2005;106:2472-2483) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Papayannopoulou and D. T. Scadden Stem-cell ecology and stem cells in motion Blood, April 15, 2008; 111(8): 3923 - 3930. [Abstract] [Full Text] [PDF] N. Giuliani, F. Morandi, S. Tagliaferri, M. Lazzaretti, G. Donofrio, S. Bonomini, R. Sala, M. Mangoni, and V. Rizzoli Production of Wnt Inhibitors by Myeloma Cells: Potential Effects on Canonical Wnt Pathway in the Bone Microenvironment Cancer Res., August 15, 2007; 67(16): 7665 - 7674. [Abstract] [Full Text] [PDF] E. Terpos, O. Sezer, P. Croucher, and M.-A. Dimopoulos Myeloma bone disease and proteasome inhibition therapies Blood, August 15, 2007; 110(4): 1098 - 1104. [Abstract] [Full Text] [PDF] N. Giuliani, F. Morandi, S. Tagliaferri, M. Lazzaretti, S. Bonomini, M. Crugnola, C. Mancini, E. Martella, L. Ferrari, A. Tabilio, et al. The proteasome inhibitor bortezomib affects osteoblast differentiation in vitro and in vivo in multiple myeloma patients Blood, July 1, 2007; 110(1): 334 - 338. [Abstract] [Full Text] [PDF] Y. Li, G. Toraldo, A. Li, X. Yang, H. Zhang, W.-P. Qian, and M. N. Weitzmann B cells and T cells are critical for the preservation of bone homeostasis and attainment of peak bone mass in vivo Blood, May 1, 2007; 109(9): 3839 - 3848. [Abstract] [Full Text] [PDF] T. Standal, N. Abildgaard, U.-M. Fagerli, B. Stordal, O. Hjertner, M. Borset, and A. Sundan HGF inhibits BMP-induced osteoblastogenesis: possible implications for the bone disease of multiple myeloma Blood, April 1, 2007; 109(7): 3024 - 3030. [Abstract] [Full Text] [PDF] S. Yaccoby, W. Ling, F. Zhan, R. Walker, B. Barlogie, and J. D. Shaughnessy Jr Antibody-based inhibition of DKK1 suppresses tumor-induced bone resorption and multiple myeloma growth in vivo Blood, March 1, 2007; 109(5): 2106 - 2111. [Abstract] [Full Text] [PDF] N. Giuliani, V. Rizzoli, and G. D. Roodman Multiple myeloma bone disease: pathophysiology of osteoblast inhibition Blood, December 15, 2006; 108(13): 3992 - 3996. [Abstract] [Full Text] [PDF] G. D. Roodman New potential targets for treating myeloma bone disease. Clin. Cancer Res., October 15, 2006; 12(20): 6270s - 6273s. [Abstract] [Full Text] [PDF] R. N. Pearse Wnt antagonism in multiple myeloma: a potential cause of uncoupled bone remodeling. Clin. Cancer Res., October 15, 2006; 12(20): 6274s - 6278s. [Abstract] [Full Text] [PDF]

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