Department of Orthopaedics, University of Maryland, School of Medicine, Baltimore, MD 21201, USA.
Biochem Biophys Res Commun. 2010 Nov 12;402(2):258-64. doi: 10.1016/j.bbrc.2010.10.011. Epub 2010 Oct 8.
The purpose of this study was to characterize the molecular phenotype that occurs during the profound morphological shift of cultured osteogenic cells upon treatment with fibroblast growth factor-2 (FGF2). A time course of treatment with FGF2 was performed on an osteoblast cell line, primary bone marrow stromal cells and an osteocyte-like cell line. Morphologic changes were recorded, and gene profiling was carried out by real time PCR. By 8h of FGF2 treatment, there is a striking morphological shift of osteoblast and stromal cells to an elongated dendritic-like morphology that is remindful of osteocytes. In osteoblasts treated with FGF2, this morphologic shift is preceded by an induction of several osteocyte markers, including dentin matrix protein 1 (>20-fold) and E11 (>5-fold). There is a transient increase in the gene expression of sclerostin (3.5-fold) and PHEX (2.5-fold). Sclerostin regulation by FGF2 is complex, as gene expression becomes markedly inhibited by FGF2 at times points after 8h of treatment before rebounding at day 12. Analogous modulation of osteocyte markers is seen in bone marrow stromal cells and MLO-Y4 osteocyte-like cells. In conclusion, this study shows that FGF2 can regulate the transition of osteogenic cells towards the osteocyte lineage, as well as, regulate the expression of critical genes in osteocytes.
本研究旨在描述成骨细胞在碱性成纤维细胞生长因子-2（FGF2）作用下发生深刻形态变化时的分子表型。用 FGF2 对成骨细胞系、原代骨髓基质细胞和骨细胞样细胞系进行时间进程处理。记录形态变化，并通过实时 PCR 进行基因谱分析。FGF2 处理 8 小时后，成骨细胞和基质细胞发生显著的形态变化，向拉长的树突状形态转变，类似于骨细胞。在 FGF2 处理的成骨细胞中，这种形态变化之前会诱导几个骨细胞标志物，包括牙本质基质蛋白 1（>20 倍）和 E11（>5 倍）。骨钙素（3.5 倍）和 PHEX（2.5 倍）的基因表达短暂增加。FGF2 对骨钙素的调节非常复杂，因为在 8 小时后，基因表达在处理后时间点被 FGF2 显著抑制，然后在第 12 天反弹。在骨髓基质细胞和 MLO-Y4 骨细胞样细胞中也观察到类似的骨细胞标志物的调节。总之，本研究表明，FGF2 可以调节成骨细胞向骨细胞系的转化，并调节骨细胞中关键基因的表达。
