Bone Sialoprotein Enhances Migration of Bone Marrow Stromal Cells Through Matrices by Bridging MMP-2 to αvβ3-Integrin

Authors

  • Abdullah Karadag,

    1. Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
    2. Academic Unit of Urology, Division of Clinical Sciences, University of Sheffield Medical School, Sheffield, United Kingdom
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  • Larry W Fisher

    Corresponding author
    1. Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
    • Larry W Fisher, PhD Craniofacial and Skeletal Diseases Branch Building 30, Room 228, 9000 Rockville Pike National Institute of Dental and Craniofacial Research NIH, DHHS Bethesda, MD 20892–4320, USA
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  • The authors state that they have no conflicts of interest.

  • Published online on July 17, 2006;

Abstract

BMSCs migrate through matrix barriers and differentiate into osteoblasts. BSP enhances osteogenic cell migration through basement membrane and collagen matrices in vitro by localizing MMP-2 on the cell surface through αvβ3-integrin.

Introduction: The specific mechanisms by which bone marrow stromal cells (BMSCs) leave their primary sites, move through matrices encountered during homing to their site of final differentiation, and remove preexisting matrices in preparation for bone matrix production are not well understood.

Materials and Methods: The enhanced migration of human osteoblast precursor cells through matrix barriers by bone sialoprotein (BSP) was studied by a modified Boyden-chamber assay. The bridging of normally soluble matrix metalloproteinase 2 (MMP-2) to the cell surface receptor, αvβ3-integrin, by BSP was analyzed by flow cytometry.

Results: BSP enhanced the in vitro passage of BMSCs and pre-osteoblasts through matrix barriers (Matrigel and denatured type I collagen) in a dose-dependent manner. An intact ArgGlyAsp (RGD) was required in the BSP for enhanced migration through the barriers but was not sufficient, as shown by the inactivity of two other SIBLING (Small Integrin-Binding LIgand, N-linked Glycoprotein) family members, osteopontin and dentin matrix protein-1. The specificity of the BSP enhancement activity was apparently caused by this molecule's ability to bridge MMP-2 to the cell surfaces.

Conclusions: Pre-osteoblasts and their BMSC precursors may use MMP-2/BSP/integrin complexes to disrupt matrix barriers during migration to their final destinations in vivo.

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