TAZ (transcriptional coactivator with PDZ-binding motif) is a transcriptional modulator that regulates mesenchymal stem cell differentiation. It stimulates osteogenic differentiation while inhibiting adipocyte differentiation. FGFs (fibroblast growth factors) stimulate several signaling proteins to regulate their target genes, which are involved in cell proliferation, differentiation, and cell survival. Within this family, FGF2 stimulates osteoblast differentiation though a mechanism that is largely unknown. In this report, we show that TAZ mediates FGF2 signaling in osteogenesis. We observed that FGF2 increases TAZ expression by stimulating its mRNA expression. Depletion of TAZ using small hairpin RNA blocked FGF2-mediated osteogenic differentiation. FGF2 induced TAZ expression was stimulated by ERK (extracellular signal-regulated kinase) activation and the inhibition of ERK blocked TAZ expression. FGF2 increased nuclear localization of TAZ and, thus, facilitated the interaction of TAZ and Runx2, activating Runx2-mediated gene transcription. Taken together, these results suggest that TAZ is an important mediator of FGF2 signaling in osteoblast differentiation.
Keywords: ERK; FGF2; MAPK; MAPK kinase; MEK; Osteogenesis; PKC; Runx2; TAZ; YAP; Yes-associated protein; extracellular signal-regulated kinase; fibroblast growth factor 2; mitogen activated protein kinases; protein kinase C; transcriptional co-activator with PDZ binding domain.
© 2013.