Basic fibroblast growth factor increases IFT88 expression in chondrocytes.

Abstract

Intraflagellar transport protein 88 (IFT88) is protein crucial for the assembly and maintenance of primary cilia in chondrocytes. Primary cilia regulate mechanical and chemical signals in chondrocytes; however, the effects of cytokines on IFT88 expression and cilia formation and maintenance remain to be elucidated. Therefore, the role of basic fibroblast growth factor (bFGF) on IFT88 expression were examined in the ATDC5 murine chondrocytic line, in order to investigate the signaling pathways involved in this process. bFGF treatment upregulated IFT88 expression in a dose- and time-dependent manner in ATDC5 cells. The effects of bFGF on IFT88 protein expression were suppressed in the presence of the extracellular signal-regulated protein kinase (ERK) inhibitor PD0325901 and the FGF receptor inhibitor BGJ398. In addition, treatment with IFT88-trageting small interfering (si)RNA downregulated the protein expression of IFT88 and ERK, thus suggesting that the ERK signaling pathway may be involved in the regulation of IFT88 expression in ATDC5 cells. bFGF treatment increased the number of ciliated ATDC5 cells and primary cultured chondrocytes. Downregulation of IFT88 expression by PD0325901, BGJ398, or IFT88-targeting siRNA was revealed to reduce the number of ciliated cells. bFGF also upregulated the mRNA and protein expression of IFT88 in primary cultured chondrocytes. In conclusion, the findings of the present study suggested that bFGF may enhance the expression of IFT88, and promote primary cilia development, through the mitogen-activated protein kinase/ERK-mediated pathway in chondrocytes.