Indexed on: 25 Jan '17Published on: 25 Jan '17Published in: Journal of cell science
Extracellular matrix (ECM) stiffness regulates the lineage commitment of mesenchymal stem cells (MSCs). Although cells sense ECM stiffness through focal adhesion, how cells sense ECM stiffness and regulate ECM stiffness-dependent differentiation remains largely unclear. In this study, we show that cytoskeletal focal adhesion protein vinculin plays a critical role in the ECM stiffness-dependent adipocyte differentiation of MSCs. ST2 mouse MSCs differentiate into adipocytes and osteoblasts in an ECM stiffness-dependent manner. We find that a rigid ECM increases cytoskeleton-associated vinculin and promotes the nuclear localization and activity of transcriptional coactivator Yes-associated protein (YAP)/transcriptional coactivator with a PDZ-binding motif (TAZ). Vinculin is necessary for enhanced nuclear localization and activity of YAP/TAZ on the rigid ECM but it does not affect the phosphorylation of a YAP/TAZ kinase, LATS1. Furthermore, vinculin depletion promotes the differentiation into adipocytes on rigid ECM, while it inhibits the differentiation into osteoblasts. Finally, TAZ knockdown was less effective for adipocyte differentiation in vinculin depleted cells than control cells. These results suggest that vinculin promotes the nuclear localization of transcription factor TAZ to inhibit the adipocyte differentiation on rigid ECM.