| http://purl.uniprot.org/citations/16927379 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16927379 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16927379 | http://www.w3.org/2000/01/rdf-schema#comment | "Human mesenchymal stem cell (hMSC) differentiation into osteoblasts and the signaling events involved are poorly understood. We recently established that contact with specific extracellular matrix (ECM) proteins, in particular laminin-5, is sufficient to induce an osteogenic phenotype in hMSC through an extracellular signal-related kinase (ERK)-dependent pathway. Activation of ERK 1/2 by laminin-5 induces phosphorylation of the runx2/cbfa-1 transcription factor that controls osteogenic gene expression. We hypothesized that focal adhesion kinase (FAK) mediated signaling pathways supply a link between cell surface integrin-ECM binding and activation of ERK 1/2, and that laminin-5 promotes its osteogenic effects through this pathway. To test this hypothesis, we plated hMSC on a laminin-5 matrix in the presence or absence of FAK-specific small inhibitory RNAs (siRNA), and assayed for phosphorylation of runx2/cbfa-1 as well as expression of established osteogenic differentiation markers (bone sialoprotein, osteocalcin, alkaline phosphatase, calcium deposition, and mineral:matrix ratio). We found that siRNA treatment reduced total endogenous FAK protein by approximately 40%, and reduced FAK phosphorylation on Y397 by approximately 33% in cells plated on laminin-5 for 30 min. SiRNA treated cells exhibited a decrease in ERK 1/2 phosphorylation after 1 h, and reduced serine/threonine phosphorylation of Runx2/Cbfa-1 after 8 days. Finally, FAK inhibition blocked osteogenic differentiation of hMSC, as assessed by lowered expression of osteogenic genes (RT-PCR), decreased alkaline phosphatase activity, greatly reduced calcium deposition, and a lower mineral:matrix ratio after 28 days in culture. These results establish FAK as an important mediator of laminin-5-induced osteogenic differentiation of hMSC."xsd:string |
| http://purl.uniprot.org/citations/16927379 | http://purl.org/dc/terms/identifier | "doi:10.1002/jcb.21074"xsd:string |
| http://purl.uniprot.org/citations/16927379 | http://purl.org/dc/terms/identifier | "doi:10.1002/jcb.21074"xsd:string |
| http://purl.uniprot.org/citations/16927379 | http://purl.uniprot.org/core/author | "Boskey A."xsd:string |
| http://purl.uniprot.org/citations/16927379 | http://purl.uniprot.org/core/author | "Boskey A."xsd:string |
| http://purl.uniprot.org/citations/16927379 | http://purl.uniprot.org/core/author | "Klees R.F."xsd:string |
| http://purl.uniprot.org/citations/16927379 | http://purl.uniprot.org/core/author | "Klees R.F."xsd:string |
| http://purl.uniprot.org/citations/16927379 | http://purl.uniprot.org/core/author | "Plopper G.E."xsd:string |
| http://purl.uniprot.org/citations/16927379 | http://purl.uniprot.org/core/author | "Plopper G.E."xsd:string |
| http://purl.uniprot.org/citations/16927379 | http://purl.uniprot.org/core/author | "Salasznyk R.M."xsd:string |
| http://purl.uniprot.org/citations/16927379 | http://purl.uniprot.org/core/author | "Salasznyk R.M."xsd:string |
| http://purl.uniprot.org/citations/16927379 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/16927379 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/16927379 | http://purl.uniprot.org/core/name | "J. Cell. Biochem."xsd:string |
| http://purl.uniprot.org/citations/16927379 | http://purl.uniprot.org/core/name | "J. Cell. Biochem."xsd:string |
| http://purl.uniprot.org/citations/16927379 | http://purl.uniprot.org/core/pages | "499-514"xsd:string |
| http://purl.uniprot.org/citations/16927379 | http://purl.uniprot.org/core/pages | "499-514"xsd:string |
| http://purl.uniprot.org/citations/16927379 | http://purl.uniprot.org/core/title | "Activation of FAK is necessary for the osteogenic differentiation of human mesenchymal stem cells on laminin-5."xsd:string |
| http://purl.uniprot.org/citations/16927379 | http://purl.uniprot.org/core/title | "Activation of FAK is necessary for the osteogenic differentiation of human mesenchymal stem cells on laminin-5."xsd:string |
| http://purl.uniprot.org/citations/16927379 | http://purl.uniprot.org/core/volume | "100"xsd:string |
| http://purl.uniprot.org/citations/16927379 | http://purl.uniprot.org/core/volume | "100"xsd:string |
| http://purl.uniprot.org/citations/16927379 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/16927379 |
| http://purl.uniprot.org/citations/16927379 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/16927379 |