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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 7, 2004 Accepted July 25, 2004 Immature dendritic cell transdifferentiation into osteoclasts: a novel pathway sustained by the rheumatoid arthritis microenvironment Aymeric Rivollier, Marlene Mazzorana, Jacques Tebib, Muriel Piperno, Tarik Aitsiselmi, Chantal Rabourdin-Combe, Pierre Jurdic, and Christine Servet-Delprat* ences Gerland,INSERM U503, Universite Claude Bernard Lyon I, Lyon, France UMR CNRS 5161, Lyon, France Service de Rhumatologie, Centre Hospitalier Lyon Sud, Pierre-Benite, Lyon, France Centre Livet, Lyon, France * Corresponding author; email: servet{at}cervi-lyon.inserm.fr. Dendritic cells, the mononuclear cells which initiate immune response, and osteoclasts, the multinucleated bone-resorbing cells, are derived from monocyte/macrophage precursor cells. GM-CSF and M-CSF reciprocally regulate the differentiation of both lineages in mouse. Using human monocyte-derived dendritic cells generated in vitro, we show that immature dendritic cells transdifferentiate into functional osteoclasts in the presence of M-CSF and 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, dendritic cell 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 pro-inflammatory cytokines such as IL-1 or TNF-, as well as components of the extracellular matrix such as hyaluronic acid. Our data therefore suggest that dendritic cell-derived osteoclasts 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 dendritic cells and chronic lytic bone lesions. 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. J. de Vries, T. Schoenmaker, B. Hooibrink, P. J. M. Leenen, and V. Everts Myeloid blasts are the mouse bone marrow cells prone to differentiate into osteoclasts J. Leukoc. Biol., June 1, 2009; 85(6): 919 - 927. [Abstract] [Full Text] [PDF] X. 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