Cooperation of Matrix Metalloproteinases with the RhoA/Rho Kinase and Mitogen‐Activated Protein Kinase Kinase‐1/Extracellular Signal‐Regulated Kinase Signaling Pathways Is Required for the Sphingosine‐1‐Phosphate‐Induced Mobilization of Marrow‐Derived Stromal Cells

• Published in: Stem cells (Dayton, Ohio) Ohio), 2006-11, Vol.24 (11), p.2557-2565
• Main Authors: Meriane, Mayya, Duhamel, Stéphanie, Lejeune, Laurence, Galipeau, Jacques, Annabi, Borhane
• Format: Article
• Language: English
• Subjects: Actin cytoskeleton; Actin Cytoskeleton - drug effects; Actin Cytoskeleton - metabolism; Amides - pharmacology; Animals; Bone Marrow Cells - drug effects; Bone Marrow Cells - enzymology; Bone Marrow Cells - metabolism; Cell migration; Cell Shape - drug effects; Cells, Cultured; Chemotaxis - drug effects; Dose-Response Relationship, Drug; Enzyme Inhibitors - pharmacology; Female; Flavonoids - pharmacology; Focal Adhesion Protein-Tyrosine Kinases - metabolism; Hydroxamic Acids; Indoles - pharmacology; Intracellular Signaling Peptides and Proteins - antagonists & inhibitors; Intracellular Signaling Peptides and Proteins - metabolism; Lysophospholipids - pharmacology; MAP Kinase Kinase 1 - antagonists & inhibitors; MAP Kinase Kinase 1 - metabolism; MAP Kinase Signaling System - drug effects; Marrow‐derived stromal cells; Matrix Metalloproteinase Inhibitors; Matrix metalloproteinases; Matrix Metalloproteinases - metabolism; Mice; Mice, Inbred C57BL; Paxillin - metabolism; Phosphorylation; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - metabolism; Pyridines - pharmacology; Rho GTPases; rho-Associated Kinases; rhoA GTP-Binding Protein - metabolism; ROCK MEK1/ERK; Sphingosine - analogs & derivatives; Sphingosine - pharmacology; Sphingosine‐1‐phosphate; Stromal Cells - enzymology; Stromal Cells - metabolism
• ISSN: 1066-5099; 1549-4918
• DOI: 10.1634/stemcells.2006-0209

The ease of isolation and ex vivo culture of marrow‐derived stromal cells (MSCs) from adult bone marrow renders them a very promising source of adult stem cells for gene transfer and cell therapy. However, little is known about the signaling pathways that control their in vivo mobilization and subsequent biodistribution. Platelet‐derived sphingosine‐1‐phosphate (S1P), a bioactive lipid that acts via G‐protein‐coupled‐receptors, exerts strong chemoattraction upon MSCs through yet‐uncharacterized signaling pathways. We show that the S1P‐induced migration and morphological changes of MSCs in vitro require the activities of extracellular signal‐regulated kinase (ERK), Rho kinase (ROCK), and matrix metalloproteinase (MMP) signaling molecules. Specifically, S1P‐induced remodeling of the MSC cytoskeleton led to the rapid (