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Myeloma

Soluble decoy receptor 3 modulates the survival and formation of osteoclasts from multiple myeloma bone disease patients

Leukemia volume 23, pages 2139–2146 (2009)Cite this article

Abstract

Decoy receptor 3 (DcR3), a member of the tumor necrosis factor (TNF) receptor superfamily, is known to be involved in cell survival and osteoclast (OC) formation. In this study, we show that malignant plasma cells and T lymphocytes from multiple myeloma (MM) bone disease patients, as well as Karpas 909, a human myeloma cell line, directly produce DcR3. By interacting with FasL, this molecule could inhibit OC apoptosis. In fact, the use of a neutralizing anti-DcR3 antibody induces a reduction of cell viability with a consequent increase of apoptotic cell number, the activation of caspase-8 and -3, and DNA fragmentation. Furthermore, we show that DcR3 supports OC formation in samples from MM patients through the upregulation of RANKL and TNFα by T lymphocytes and only TNFα by CD14+ cells. In conclusion, our data provide the first evidence of the expression of DcR3 in MM, and the involvement of this molecule in supporting the survival and formation of OCs from MM bone disease patients. The production of DcR3 by T lymphocytes confers these cells a role in the pathogenesis of bone disease associated with MM.

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Acknowledgements

We thank Ministero dell'Istruzione Università e Ricerca (ex 60% grant to Maria Grano) and Multiple Myeloma Research Foundation (MMRF) for financial support, and Ms MVC Pragnell, BA, for linguistic help.

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Authors and Affiliations

  1. Department of Human Anatomy and Histology, University of Bari, Bari, Italy

    S Colucci, G Brunetti, A Oranger, M Centonze, R Tamma, A Zallone & M Grano

  2. Department of Biomedical Science, University of Foggia, Foggia, Italy

    G Mori

  3. Department of Orthopaedic Surgery, University of Bari, Bari, Italy

    C Mori

  4. Clinica Reumatologica ‘M. Carrozzo’, University of Foggia, Foggia, Italy

    F P Cantatore

  5. Department of Pathology, Hematology Section, University of Bari, Bari, Italy

    R Rizzi & V Liso

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  1. S Colucci
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Correspondence to M Grano.

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Colucci, S., Brunetti, G., Mori, G. et al. Soluble decoy receptor 3 modulates the survival and formation of osteoclasts from multiple myeloma bone disease patients. Leukemia 23, 2139–2146 (2009). https://doi.org/10.1038/leu.2009.136

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