Laminin-5 induces osteogenic gene expression in human mesenchymal stem cells through an ERK-dependent pathway

The laminin family of proteins is critical for managing a variety of cellular activities including migration, adhesion, and differentiation. In bone, the roles of laminins in controlling osteogenic differentiation of human mesenchymal stem cells (hMSC) are unknown. We report here that laminin-5 is f...

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Bibliographic Details
Published in:Molecular biology of the cell 2005-02, Vol.16 (2), p.881-890
Main Authors: Klees, Robert F, Salasznyk, Roman M, Kingsley, Karl, Williams, William A, Boskey, Adele, Plopper, George E
Format: Article
Language:English
Subjects:
Biomarkers
Blotting, Western
Calcium - analysis
Calcium - metabolism
Cell Adhesion
Cell Adhesion Molecules - genetics
Cell Adhesion Molecules - metabolism
Cell Differentiation
Cell Movement
Cells, Cultured
Core Binding Factor Alpha 1 Subunit
DNA-Binding Proteins - metabolism
Enzyme Inhibitors - pharmacology
Flavonoids - pharmacology
Gene Expression
Humans
Immunohistochemistry
Integrin alpha3beta1 - metabolism
Kalinin
Mesenchymal Stem Cells - cytology
Mitogen-Activated Protein Kinase 3 - drug effects
Mitogen-Activated Protein Kinase 3 - metabolism
Osteogenesis
Phosphorylation
Precipitin Tests
Reverse Transcriptase Polymerase Chain Reaction
Spectroscopy, Fourier Transform Infrared
Time Factors
Transcription Factor AP-2
Transcription Factors - metabolism
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Summary:The laminin family of proteins is critical for managing a variety of cellular activities including migration, adhesion, and differentiation. In bone, the roles of laminins in controlling osteogenic differentiation of human mesenchymal stem cells (hMSC) are unknown. We report here that laminin-5 is found in bone and expressed by hMSC. hMSC isolated from bone synthesize laminin-5 and adhere to exogenous laminin-5 through alpha3beta1 integrin. Adhesion to laminin-5 activates extracellular signal-related kinase (ERK) within 30 min and leads to phosphorylation of the osteogenic transcription factor Runx2/CBFA-1 within 8 d. Cells plated on laminin-5 for 16 d express increased levels of osteogenic marker genes, and those plated for 21 d deposit a mineralized matrix, indicative of osteogenic differentiation. Addition of the ERK inhibitor PD98059 mitigates these effects. We conclude that contact with laminin-5 is sufficient to activate ERK and to stimulate osteogenic differentiation in hMSC.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.E04-08-0695