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Blood, 15 August 2005, Vol. 106, No. 4, pp. 1232-1239. Prepublished online as a Blood First Edition Paper on April 21, 2005; DOI 10.1182/blood-2004-11-4422. This Article Full Text (PDF) All Versions of this Article: 2004-11-4422v1 106/4/1232    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 Nilsson, S. K Articles by Haylock, D. N Search for Related Content PubMed PubMed Citation Articles by Nilsson, S. K Articles by Haylock, D. N Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 19, 2004 Accepted April 13, 2005 Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells Susan K Nilsson*, Hayley M Johnston, Genevieve A Whitty, Brenda Williams, Ryan J Webb, David T Denhardt, Ivan Bertoncello, Linda J Bendall, Paul J Simmons, and David N Haylock Stem Cell Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey, USA Westmead Institute of Cancer Research, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia * Corresponding author; email: susie.nilsson{at}petermac.org. Although recent data suggests that osteoblasts play a key role within the hematopoietic stem cell (HSC) niche the mechanisms underpinning this remain to be fully defined. The studies described herein examine the role in hematopoiesis of Osteopontin (Opn), a multi domain, phosphorylated glycoprotein, synthesised by osteoblasts, with well described roles in cell adhesion, inflammatory responses, angiogenesis, and tumor metastasis. We demonstrate a previously unrecognised critical role for Opn in regulation of the physical location and proliferation of HSC. Within marrow, Opn expression is restricted to the endosteal bone surface and contributes to HSC trans-marrow migration toward the endosteal region, as demonstrated by the markedly aberrant distribution of HSC in Opn-/- mice post transplantation. Primitive hematopoietic cells demonstrate specific adhesion to Opn in vitro via 1 integrin. Furthermore, exogenous Opn potently suppresses the proliferation of primitive HPC in vitro, the physiological relevance of which is demonstrated by the markedly enhanced cycling of HSC in Opn-/- mice. 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