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Blood, 1 November 2005, Vol. 106, No. 9, pp. 3160-3165. Prepublished online as a Blood First Edition Paper on July 19, 2005; DOI 10.1182/blood-2004-12-4940. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-12-4940v1 106/9/3160    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 Oshima, T. Articles by Matsumoto, T. Search for Related Content PubMed PubMed Citation Articles by Oshima, T. Articles by Matsumoto, T. Related Collections Neoplasia Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Myeloma cells suppress bone formation by secreting a soluble Wnt inhibitor, sFRP-2 Takashi Oshima, Masahiro Abe, Jin Asano, Tomoko Hara, Kenichi Kitazoe, Etsuko Sekimoto, Yoichi Tanaka, Hironobu Shibata, Toshihiro Hashimoto, Shuji Ozaki, Shinsuke Kido, Daisuke Inoue, and Toshio Matsumoto From the Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, Tokushima, Japan. Multiple myeloma (MM) develops devastating bone destruction with enhanced bone resorption and suppressed bone formation. In contrast to enhanced osteoclastogenesis, little is known about the mechanism of impaired bone formation in MM. Because a canonical Wingless-type (Wnt) signaling pathway has recently been shown to play an important role in osteoblast differentiation, we examined whether MM cells affect a canonical Wnt pathway to suppress bone formation. Conditioned media from RPMI8226 and U266 MM cell lines and primary MM cells suppressed in vitro mineralization as well as alkaline phosphatase activity in osteoblasts induced by bone morphogenetic protein 2 (BMP-2). These cell lines constitutively produced a soluble Wnt inhibitor, secreted Frizzled-related protein 2 (sFRP-2), but not other Wnt inhibitors including sFRP-1, sFRP-3, and dickkopf 1 (DKK-1) at the protein level. Most MM cells from patients with advanced bone destructive lesions also expressed sFRP-2. Furthermore, exogenous sFRP-2 suppressed osteoblast differentiation induced by BMP-2, and immunodepletion of sFRP-2 significantly restored mineralized nodule formation in vitro, suggesting a predominant role for MM cell-derived sFRP-2 in the impairment of bone formation by MM. Thus, in addition to enhanced osteolysis, MM cells also suppress bone formation at least in part through an inhibition of the canonical Wnt pathway by secreting sFRP-2. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. D. Ma, C. Park, H. Zhao, K. A. Oduro Jr, X. Tu, F. Long, P. M. Allen, S. L. Teitelbaum, and K. Choi Defects in osteoblast function but no changes in long-term repopulating potential of hematopoietic stem cells in a mouse chronic inflammatory arthritis model Blood, November 12, 2009; 114(20): 4402 - 4410. [Abstract] [Full Text] [PDF] A. Pennisi, W. Ling, X. Li, S. Khan, J. D. Shaughnessy Jr, B. Barlogie, and S. 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