Stem Cell Differentiation Depending on Different Surfaces - Tissue Engineering: Cell-Surface Interactions for Tissue Culture - page 276

Biomaterial

Extracellular

Integrin

Cytoplasm

FAK

ERK 1/2

ERK 1/2

Nucleus

RUN X2

Fig. 4 The focal adhesion kinase pathway. The first step in the transmission of extracellular
forces is the cell adhesion on the substrate modulated by integrins. The integrins activate the
intracellular focal adhesion kinase and via multiple phosphorylation steps the extracellular-
signal-regulated kinase is translocated into the nucleus, where it affects the expression of specific
transcription factors, such as Runx2

transmission. Diverse protein networks dynamically link the artificial ECM to the
intracellular actin cytoskeleton. These supramolecular structures are called focal
adhesions. Proteins joining the focal adhesion complex have the ability to translate
mechanical forces into biochemical signals and pass the information to the
nucleus. However, the exact signaling pathways linking focal adhesion with the
commitment of MSC are not completely understood. Nevertheless, several studies
suggest that for osteogenic lineage commitment integrins activate the focal
adhesion kinase, which influences cellular events through adhesion-dependent
phosphorylation of downstreaming signaling molecules, especially the extracel-
lular-signal-regulated kinase (ERK) [ 86 ]. The ERK is a member of the mitogen-
activated protein kinase family, which acts as a mediator of cellular differentiation.