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Blood, 1 April 2007, Vol. 109, No. 7, pp. 3024-3030. Prepublished online as a Blood First Edition Paper on November 30, 2006; DOI 10.1182/blood-2006-07-034884. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-07-034884v1 109/7/3024    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 Standal, T. Articles by Sundan, A. Search for Related Content PubMed PubMed Citation Articles by Standal, T. Articles by Sundan, A. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA HGF inhibits BMP-induced osteoblastogenesis: possible implications for the bone disease of multiple myeloma Therese Standal1, Niels Abildgaard2, Unn-Merete Fagerli1, Berit Stordal1, Øyvind Hjertner1,3, Magne Borset1,4, and Anders Sundan1 1 Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway; 2 Department of Haematology, Odense University Hospital, Denmark; 3 Department of Hematology and 4 Department of Immunology and Transfusion Medicine, St Olav University Hospital, Trondheim, Norway The bone disease in multiple myeloma is caused by an uncoupling of bone formation from bone resorption. A key difference between patients with and patients without osteolytic lesion is that the latter have fewer and less active osteoblasts. Hepatocyte growth factor (HGF) is often produced by myeloma cells and is found at high concentrations in the bone marrow of patients with multiple myeloma. Here we show that HGF inhibited bone morphogenetic protein (BMP)–induced in vitro osteoblastogenesis. Thus, HGF inhibited BMP-induced expression of alkaline phosphatase in human mesenchymal stem cells (hMSCs) and the murine myoid cell line C2C12, as well as mineralization by hMSCs. Furthermore, the expression of the osteoblast-specific transcription factors Runx2 and Osterix was reduced by HGF treatment. HGF promoted proliferation of hMSCs, and the BMP-induced halt in proliferation was overridden by HGF, keeping the cells in a proliferative, undifferentiating state. BMP-induced nuclear translocation of receptor-activated Smads was inhibited by HGF, providing a possible explanation of how HGF inhibits BMP signaling. The in vitro data were supported by the observation of a negative correlation between HGF and a marker of osteoblast activity, bone-specific alkaline phosphatase (rho = –0.45, P = .008), in sera from 34 patients with myeloma. These observations suggest that HGF inhibits bone formation in multiple myeloma. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. C. Johnson, S. Corthals, C. Ramos, A. Hoering, K. Cocks, N. J. Dickens, J. Haessler, H. Goldschmidt, J. A. Child, S. E. Bell, et al. Genetic associations with thalidomide mediated venous thrombotic events in myeloma identified using targeted genotyping Blood, December 15, 2008; 112(13): 4924 - 4934. [Abstract] [Full Text] [PDF] R. U. Holt, U.-M. Fagerli, V. Baykov, T. B. Ro, H. Hov, A. Waage, A. Sundan, and M. Borset Hepatocyte growth factor promotes migration of human myeloma cells Haematologica, April 1, 2008; 93(4): 619 - 622. [Abstract] [Full Text] [PDF]

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