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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.
 Previous Article | Table of Contents | Next Article 
HEMATOPOIESIS
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
From the Stem Cell Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; the Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ; the Cancer Institute of New Jersey, Piscataway, NJ; and the Westmead Institute of Cancer Research, Westmead Millennium Institute, University of Sydney, New South Wales, Australia.
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 multidomain, phosphorylated glycoprotein, synthesized by osteoblasts, with well-described roles in cell adhesion, inflammatory responses, angiogenesis, and tumor metastasis. We demonstrate a previously unrecognized critical role for Opn in regulation of the physical location and proliferation of HSCs. Within marrow, Opn expression is restricted to the endosteal bone surface and contributes to HSC transmarrow migration toward the endosteal region, as demonstrated by the markedly aberrant distribution of HSCs in Opn–/– mice after transplantation. Primitive hematopoietic cells demonstrate specific adhesion to Opn in vitro via  1 integrin. Furthermore, exogenous Opn potently suppresses the proliferation of primitive HPCs in vitro, the physiologic relevance of which is demonstrated by the markedly enhanced cycling of HSC in Opn–/– mice. These data therefore provide strong evidence that Opn is an important component of the HSC niche which participates in HSC location and as a physiologic-negative regulator of HSC proliferation.
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