Myeloma cells suppress osteoblasts through sclerostin secretion

S. Colucci, G. Brunetti, A. Oranger, G. Mori, F. Sardone, G. Specchia, E. Rinaldi, P. Curci, V. Liso, G. Passeri, A. Zallone, R. Rizzi, M. Grano

Research output: Contribution to journalArticle

Abstract

Wingless-type (Wnt) signaling through the secretion of Wnt inhibitors Dickkopf1, soluble frizzled-related protein-2 and -3 has a key role in the decreased osteoblast (OB) activity associated with multiple myeloma (MM) bone disease. We provide evidence that another Wnt antagonist, sclerostin, an osteocyte-expressed negative regulator of bone formation, is expressed by myeloma cells, that is, human myeloma cell lines (HMCLs) and plasma cells (CD138+ cells) obtained from the bone marrow (BM) of a large number of MM patients with bone disease. We demonstrated that BM stromal cells (BMSCs), differentiated into OBs and co-cultured with HMCLs showed, compared with BMSCs alone, reduced expression of major osteoblastic-specific proteins, decreased mineralized nodule formation and attenuated the expression of members of the activator protein 1 transcription factor family (Fra-1, Fra-2 and Jun-D). Moreover, in the same co-culture system, the addition of neutralizing anti-sclerostin antibodies restored OB functions by inducing nuclear accumulation of β-catenin. We further demonstrated that the upregulation of receptor activator of nuclear factor κ-B ligand and the downregulation of osteoprotegerin in OBs were also sclerostin mediated. Our data indicated that sclerostin secretion by myeloma cells contribute to the suppression of bone formation in the osteolytic bone disease associated to MM.

Original languageEnglish
Article numbere27
JournalBlood Cancer Journal
Volume1
Issue number6
DOIs
Publication statusPublished - Jun 2011

Keywords

  • Multiple myeloma
  • Myeloma cells
  • Osteoblasts
  • Osteolysis
  • Sclerostin

ASJC Scopus subject areas

  • Oncology
  • Hematology

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    Colucci, S., Brunetti, G., Oranger, A., Mori, G., Sardone, F., Specchia, G., Rinaldi, E., Curci, P., Liso, V., Passeri, G., Zallone, A., Rizzi, R., & Grano, M. (2011). Myeloma cells suppress osteoblasts through sclerostin secretion. Blood Cancer Journal, 1(6), [e27]. https://doi.org/10.1038/bcj.2011.22