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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 4, 2005 Accepted May 23, 2005 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 Laboratory of Hematology, Chair of Hematology and BMT Center, Department of Internal Medicine and Biomedical Science, University of Parma, Parma, Italy Pathology, University of Parma, Parma, Italy Department of Experimental Medicine, University of Parma, Parma, Italy Department of Human Anatomy and Histology, University of Bari, Bari, Italy Ematologia, Bolzano, Italy * Corresponding author; email: n_giuliani{at}yahoo.com. The 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 the osteoblast formation and differentiation and the potential role of the critical osteoblast transcription factor Runx2/Cbfa1 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 and collagen I mRNA and protein expression and on Runx2/Cbfa1 activity by human pre-osteoblastic cells was observed in co-cultures with myeloma cells. The inhibitory effect was more pronounced in the cell-to-cell contact conditions as compared to those without the contact and involved VLA-4 integrin system. Among the soluble osteoblast inhibitors screened we show the potential contribute of IL-7 in the inhibitory effect on osteoblast formation and Runx2/Cbfa1 activity by human myeloma cells in co-culture. 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 MM patients with osteolytic lesions as compared to those without bone lesions suggesting the critical involvement of Runx2/Cbfa1 in the decreased bone formation in MM. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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. Sezer Myeloma Bone Disease: Recent Advances in Biology, Diagnosis, and Treatment Oncologist, March 1, 2009; 14(3): 276 - 283. [Abstract] [Full Text] [PDF] J. J. Pinzone, B. M. Hall, N. K. Thudi, M. 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