ERK signaling pathways regulate the osteogenic differentiation of human mesenchymal stem cells on collagen I and vitronectin.
Adhesion to the extracellular matrix (ECM) proteins collagen I and vitronectin is sufficient to drive human mesenchymal stem cells (hMSCs) into an osteogenic differentiation pathway, but the mechanisms underlying this stimulation are not well understood. We found that addition of beta1 and alpha(v)beta3 integrin blocking antibodies inhibited ECM-induced ERK activation, while addition of the MEK inhibitor PD98059 blocked ERK activation, serine phosphorylation of the osteogenic transcription factor runx2/cbfa-1, osteogenic gene expression, and calcium deposition. These results suggest that ERK plays an important role in driving the ECM-induced osteogenic differentiation of hMSC.
Salasznyk
Roman M
RM
Department of Biology, Rensselaer Polytechnic Institute, Troy, New York 12180-3596, USA.
Klees
Robert F
RF
Hughlock
Mariah K
MK
Plopper
George E
GE
D000469:Alkaline Phosphatase / Q000096:biosynthesis / Q000235:genetics; D000906:Antibodies / Q000494:pharmacology; D002448:Cell Adhesion; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism*; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors; D019012:Integrin beta1 / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000502:physiology; D010006:Osteoblasts / Q000166:cytology; D053495:Osteopontin; D010766:Phosphorylation; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000235:genetics; D019096:Vitronectin / Q000378:metabolism*
D000906:Antibodies; D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D004791:Enzyme Inhibitors; D005419:Flavonoids; D039302:Integrin alphaVbeta3; D019012:Integrin beta1; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D019096:Vitronectin; D053495:Osteopontin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000469:Alkaline Phosphatase; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one