Graduate School, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Mol Med Rep. 2017 Nov;16(5):6590-6599. doi: 10.3892/mmr.2017.7449. Epub 2017 Sep 8.
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 theATDC5 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.
内鞭毛运输蛋白 88（IFT88）是一种对软骨细胞中初级纤毛的组装和维持至关重要的蛋白质。初级纤毛调节软骨细胞中的机械和化学信号；然而，细胞因子对 IFT88 表达以及纤毛形成和维持的影响仍有待阐明。因此，本研究旨在探讨碱性成纤维细胞生长因子（bFGF）在 ATDC5 鼠软骨细胞系中对 IFT88 表达的作用，以研究参与该过程的信号通路。bFGF 处理以剂量和时间依赖的方式上调 ATDC5 细胞中的 IFT88 表达。在存在细胞外信号调节蛋白激酶（ERK）抑制剂 PD0325901 和 FGF 受体抑制剂 BGJ398 的情况下，bFGF 对 IFT88 蛋白表达的影响受到抑制。此外，IFT88 靶向小干扰（si）RNA 的处理下调了 IFT88 和 ERK 的蛋白表达，这表明 ERK 信号通路可能参与调节 ATDC5 细胞中的 IFT88 表达。bFGF 处理增加了有纤毛的 ATDC5 细胞和原代培养软骨细胞的数量。PD0325901、BGJ398 或 IFT88 靶向 siRNA 下调 IFT88 表达被揭示可减少有纤毛细胞的数量。bFGF 还上调了原代培养软骨细胞中 IFT88 的 mRNA 和蛋白表达。综上所述，本研究结果表明，bFGF 可能通过细胞丝裂原活化蛋白激酶/ERK 介导的通路增强软骨细胞中 IFT88 的表达，并促进初级纤毛的发育。
