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Blood, 15 December 2004, Vol. 104, No. 13, pp. 4029-4037. Prepublished online as a Blood First Edition Paper on August 12, 2004; DOI 10.1182/blood-2004-01-0041. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-01-0041v1 104/13/4029    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 Rivollier, A. Articles by Servet-Delprat, C. Search for Related Content PubMed PubMed Citation Articles by Rivollier, A. Articles by Servet-Delprat, C. Related Collections Hematopoiesis and Stem Cells Immunobiology Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Immature dendritic cell transdifferentiation into osteoclasts: a novel pathway sustained by the rheumatoid arthritis microenvironment Aymeric Rivollier, Marlène Mazzorana, Jacques Tebib, Muriel Piperno, Tarik Aitsiselmi, Chantal Rabourdin-Combe, Pierre Jurdic, and Christine Servet-Delprat From the INSERM U503—Université Claude Bernard Lyon I, IFR128-Biosciences Lyon-Gerland, France; UMR CNRS 5161, Ecole Normale Superieure de Lyon, France; Service de Rhumatologie, Centre Hospitalier Lyon Sud, Pierre Bénite, France; and Centre Livet, Lyon, France. Dendritic cells (DCs), the mononuclear cells that initiate immune response, and osteoclasts, the multinucleated bone-resorbing cells, are derived from monocyte/macrophage precursor cells. Granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor (M-CSF) reciprocally regulate the differentiation of both lineages in mice. Using human monocyte-derived DCs generated in vitro, we show that immature DCs transdifferentiate into functional osteoclasts (OCs) in the presence of M-CSF and receptor activator of nuclear factor-B ligand (RANKL). Transdifferentiation operates through fusion of intermediate adherent bipolar fusiform mononuclear cells expressing CD14, CD1a, and RANKL and able to induce RANKL+ T-cell proliferation. Surprisingly, DC fusion in vitro is faster and more efficient than monocyte fusion to form multinucleated giant cells. The transdifferentiation process reported here supports the existence of a high cellular plasticity within differentiated myeloid phagocytes. Importantly, this process is greatly enhanced by rheumatoid arthritis synovial fluid and involves proinflammatory cytokines such as interleukin 1 or tumor necrosis factor , as well as components of the extracellular matrix such as hyaluronic acid. Our data therefore suggest that DC-derived OCs may be directly involved in the osteolytic lesions observed in human inflammatory bone diseases such as rheumatoid arthritis or in particular forms of Langerhans cell histiocytosis, characterized by accumulation of immature skin DCs and chronic lytic bone lesions. (Blood. 2004;104:4029-4037) 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] T. 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