Fibroblast growth factor-7 facilitates osteogenic differentiation of embryonic stem cells through the activation of ERK/Runx2 signaling

Abstract

Fibroblast growth factor-7 (FGF7) is known to regulate proliferation and differentiation of cells; however, little information is available on how FGF7 affects the differentiation of embryonic stem cells (ESCs). We examined the effects of FGF7 on proliferation and osteogenic differentiation of mouse ESCs. Exogenous FGF7 addition did not change the proliferation rate of mouse ESCs. In contrast, the addition of FGF7 facilitated the dexamethasone, ascorbic acid, and β-glycerophosphate (DAG)-induced increases in bone-like nodule formation and calcium accumulation. FGF7 also augmented mRNA expression of runt-related transcription factor-2 (Runx2), osterix, bone sialoprotein (BSP), and osteocalcin (OC) in the presence of DAG. FGF7-mediated increases in the mineralization and bone-specific gene expression were almost completely attenuated by pretreating with anti-FGF7 antibody. FGF7 treatment accelerated the DAG-induced activation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) in the cells. A pharmacological inhibitor specific to ERK, but not to JNK or p38 kinase, dramatically suppressed FGF7-mediated mineralization and accumulation of collagen and OC in the presence of DAG. This suppression was accompanied by the reduction in Runx2, osterix, BSP, and OC mRNA levels, which were increased by FGF7 in the presence of DAG. Collectively, our results suggest that FGF7 stimulates osteogenic differentiation, but not proliferation, in ESCs, by activating ERK/Runx2 signaling.