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Blood, 2 July 2009, Vol. 114, No. 1, pp. 49-59.
Prepublished online as a Blood First Edition Paper on May 5, 2009; DOI 10.1182/blood-2009-01-197988.


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Submitted January 5, 2009
Accepted April 10, 2009

Thrombin cleaved osteopontin regulates hemopoietic stem and progenitor cell functions through interactions with {alpha}9{beta}1 and {alpha}4{beta}1 integrins

Jochen Grassinger, David N Haylock, Melonie J Storan, Gemma O Haines, Brenda Williams, Genevieve A Whitty, Andrew R Vinson, Cheang Ly Be, Songhui Li, Esben S Sorensen, Patrick PL Tam, David T Denhardt, Dean Sheppard, Peter F Choong, and Susan K Nilsson*

Australian Stem Cell Centre, Clayton, Victoria, Australia
Department of Molecular Biology, University of Aarhus, Aarhus, Denmark
Embryology Unit, Children's Medical Research Institute, University of Sydney, Westmead, New South Wales, Australia
Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ, United States
University of California San Francisco, San Francisco, CA, United States
Department of Orthopaedics and University of Melbourne Department of Surgery, St. Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
Department of Pathology, University of Melbourne, Parkville, Victoria, Australia

* Corresponding author; email: susie.nilsson{at}stemcellcentre.edu.au.

Osteopontin (OPN), a multifunctional acidic glycoprotein, expressed by osteoblasts within the endosteal region of the bone marrow (BM) suppresses the proliferation of hemopoietic stem and progenitor cells and also regulates their lodgment within the BM after transplantation. Herein we demonstrate that OPN cleavage fragments are the most abundant forms of this protein within the BM. Studies aimed to determine how hemopoietic stem cells (HSCs) interact with OPN revealed for the first time that murine and human HSCs express {alpha}9{beta}1 integrin. The N-terminal thrombin cleavage fragment of OPN through its binding to the {alpha}9{beta}1 and {alpha}4{beta}1 integrins plays a key role in the attraction, retention, regulation and release of hemopoietic stem and progenitor cells to, in and from their BM niche. Thrombin cleaved OPN (trOPN) acts as a chemoattractant for stem and progenitor cells, mediating their migration in a manner that involves interaction with {alpha}9{beta}1 and {alpha}4{beta}1 integrins. In addition, in the absence of OPN there is an increased number of white blood cells and specifically stem and progenitor cells in the peripheral circulation.


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E. C. Forsberg and S. Smith-Berdan
Parsing the niche code: the molecular mechanisms governing hematopoietic stem cell adhesion and differentiation
Haematologica, November 1, 2009; 94(11): 1477 - 1481.
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