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Prepublished online as a Blood First Edition Paper on August 8, 2002; DOI 10.1182/blood-2002-04-1121. This Article Full Text (PDF) All Versions of this Article: 2002-04-1121v1 100/13/4615    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? Submitted April 19, 2002 Accepted July 22, 2002 Human myeloma cells stimulate the receptor activator of NF-KB ligand (RANKL) in T lymphocytes: a potential role in multiple myeloma bone disease Nicola Giuliani*, Simona Colla, Roberto Sala, Matteo Moroni, Mirca Lazzaretti, Silvia La Monica, Sabrina Bonomini, Magda Hojden, Gabriella Sammarelli, Sophie Barille, Regis Bataille, and Vittorio Rizzoli Department of Internal Medicine and Biomedical Science, University of Parma, Parma, Italy Department of Experimental Medicine, University of Parma, Parma, Italy Department of Pathology and Laboratory Medicine, University of Parma, Parma, Italy Institut de Biologie, INSERM Unite 463, Nantes, France * Corresponding author; email: n_giuliani{at}yahoo.com. The biological mechanisms involved in the pathogenesis of multiple myeloma (MM) bone disease are not completely understood. Recent evidence suggests that T cells may regulate bone resorption through the cross-talk between the critical osteoclastogenetic factor RANKL and IFN- that strongly suppresses osteoclastogenesis. Using a co-culture transwell system we found that human myeloma cell lines (HMCL) increased the expression and secretion of RANKL in activated T lymphocytes and similarly purified MM cells stimulated RANKL production in autologous T lymphocytes. In addition, either anti IL-6 or anti IL-7 antibody inhibited HMCL-induced RANKL over-expression. Consistently, we demonstrated that HMCL and fresh MM cells express IL-7 mRNA and secrete IL-7 in presence of IL-6 and that bone marrow (BM) IL-7 levels were significantly higher in MM patients. Moreover we found that the release of IFN- by T lymphocytes was reduced in presence of both HMCL and purified MM cells. Furthermore, in a stromal cells free system, osteoclastogenesis was stimulated by conditioned medium of T cells co-cultured with HMCL and inhibited by recombinant human osteoprotegerin (OPG) (100ng/ml-1µg/ml). Finally, RANKL mRNA was up-regulated in BM T lymphocytes of MM patients with severe osteolytic lesions suggesting that T cells could be involved at least in part in MM-induced osteolysis through the RANKL over-expression. 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] M. K. Crook and T. A. Guise RANKL: Targeting Bone and Cancer to Treat Skeletal Complications of Malignancy IBMS BoneKEy, September 1, 2009; 6(9): 323 - 338. 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