Bone sialoprotein enhances migration of bone marrow stromal cells through matrices by bridging MMP-2 to alpha(v)beta3-integrin.
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 alpha(v)beta(3)-integrin.


BACKGROUND
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.


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, alpha(v)beta(3)-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.
Karadag
Abdullah
A
Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892-4320, USA.
Fisher
Larry W
LW
D001854:Bone Marrow Cells / Q000166:cytology*; D002448:Cell Adhesion; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D003094:Collagen / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D004338:Drug Combinations; D005434:Flow Cytometry; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D058574:Integrin-Binding Sialoprotein; D007797:Laminin / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D012795:Sialoglycoproteins / Q000494:pharmacology*; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
D024042:Collagen Type I; D004338:Drug Combinations; C546871:IBSP protein, human; D039302:Integrin alphaVbeta3; D058574:Integrin-Binding Sialoprotein; D007797:Laminin; D011509:Proteoglycans; D012795:Sialoglycoproteins; C059485:matrigel; D003094:Collagen; D020778:Matrix Metalloproteinase 2