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    Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis

    Access Status
    Open access via publisher
    Authors
    Cheung, Laurence
    Strickland, D.
    Howlett, M.
    Ford, J.
    Charles, A.
    Lyons, K.
    Brigstock, D.
    Goldschmeding, R.
    Cole, C.
    Alexander, W.
    Kees, U.
    Date
    2014
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Cheung, L. and Strickland, D. and Howlett, M. and Ford, J. and Charles, A. and Lyons, K. and Brigstock, D. et al. 2014. Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis. Haematologica. 99 (7): pp. 1149-1156.
    Source Title
    Haematologica
    DOI
    10.3324/haematol.2013.102327
    ISSN
    0390-6078
    School
    School of Pharmacy
    URI
    http://hdl.handle.net/20.500.11937/59563
    Collection
    • Curtin Research Publications
    Abstract

    Hematopoiesis occurs in a complex bone marrow microenvironment in which bone marrow stromal cells provide critical support to the process through direct cell contact and indirectly through the secretion of cytokines and growth factors. We report that connective tissue growth factor (Ctgf, also known as Ccn2) is highly expressed in murine bone marrow stromal cells. In contrast, connective tissue growth factor is barely detectable in unfractionated adult bone marrow cells. While connective tissue growth factor has been implicated in hematopoietic malignancies, and is known to play critical roles in skeletogenesis and regulation of bone marrow stromal cells, its role in hematopoiesis has not been described. Here we demonstrate that the absence of connective tissue growth factor in mice results in impaired hematopoiesis. Using a chimeric fetal liver transplantation model, we show that absence of connective tissue growth factor has an impact on B-cell development, in particular from pro-B to more mature stages, which is linked to a requirement for connective tissue growth factor in bone marrow stromal cells. Using in vitro culture systems, we demonstrate that connective tissue growth factor potentiates B-cell proliferation and promotes pro-B to pre-B differentiation in the presence of interleukin-7. This study provides a better understanding of the functions of connective tissue growth factor within the bone marrow, showing the dual regulatory role of the growth factor in skeletogenesis and in stage-specific B lymphopoiesis.

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