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 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.
Klees
Robert F
RF
Department of Biology, Rensselaer Polytechnic Institute, Troy, NY 12180-3596, USA.
Salasznyk
Roman M
RM
Kingsley
Karl
K
Williams
William A
WA
Boskey
Adele
A
Plopper
George E
GE
D015415:Biomarkers; D015153:Blotting, Western; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit; D004268:DNA-Binding Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D039201:Integrin alpha3beta1 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis; D010766:Phosphorylation; D011233:Precipitin Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017550:Spectroscopy, Fourier Transform Infrared; D013997:Time Factors; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000378:metabolism; D000097794:Kalinin
D015415:Biomarkers; D002118:Calcium; D015815:Cell Adhesion Molecules; D050659:Core Binding Factor Alpha 1 Subunit; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D039201:Integrin alpha3beta1; D048052:Mitogen-Activated Protein Kinase 3; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D000097794:Kalinin; C493709:RUNX2 protein, human; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one