Induction of an osteocyte-like phenotype by fibroblast growth factor-2

• Published in: Biochemical and biophysical research communications 2010-11, Vol.402 (2), p.258-264
• Main Authors: Gupta, Rishi R., Yoo, David J., Hebert, Carla, Niger, Corinne, Stains, Joseph P.
• Format: Article
• Language: English
• Subjects: Animals; Biomarkers; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - physiology; Bone marrow stromal cell; Bone Morphogenetic Proteins - genetics; Cell Differentiation - genetics; Cells, Cultured; Connexin43; Dentin matrix protein 1; Extracellular Matrix Proteins - genetics; Fibroblast Growth Factor 2 - pharmacology; Fibroblast Growth Factor 2 - physiology; Gene Expression Profiling; Gene Expression Regulation; Genetic Markers - genetics; Glycoproteins; Mice; Osteoblast; Osteoblasts - drug effects; Osteoblasts - physiology; Osteocyte; Osteocytes - cytology; PHEX Phosphate Regulating Neutral Endopeptidase - genetics; Sclerostin
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2010.10.011

► FGF2 induces an osteocyte-like phenotype in osteoblasts and stromal cells. ► FGF2 dramatically increases gene expression of DMP1. ► FGF2 suppression of SOST may contribute to the osteoanabolic effect of FGF2 in vivo. ► DMP1 and E11 expression precedes the formation of osteocyte-like cell processes. ► Model to study osteocyte biology to complement cell lines, such as MLO-Y4 cells. 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 8 h 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 8 h 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.