Fibroblast growth factor enhances type β1 transforming growth factor gene expression in osteoblast-like cells

Abstract

Fibroblast growth factor (FGF) and type β transforming growth factor (TGFβ) are potent modulators of proliferation and differentiation in many types of cells. TGFβ acts in an autocrine manner, and the regulation of TGFβ gene expression is one of the crucial events in the control of cellular functions. This study examines FGF regulation of TGFβ1 gene expression in osteoblast-like cells. Bovine basic FGF (bFGF) increased the steady-state level of 2.5-kb TGFβ1 mRNA two- to threefold in rat osteosarcoma (ROS17/2.8) cells in a dose-dependent manner, starting at 0.1 ng/ml. The increase of the message was detectable within 3 h after the addition of bFGF, peaked at 6 h, and lasted at least up to 48 h. This effect was blocked by a protein kinase inhibitor, K252a, indicating the involvement of phosphorylation. bFGF increased the rate of TGFβ1 gene transcription estimated by nuclear run-on assay, while the stability of TGFβ1 mRNA was not altered. bFGF increased the TGFβ activity in the conditioned media, estimated by DNA synthesis inhibition assay using mink lung epithelial (CCL-64) cells. Parathyroid hormone reduced the abundance of TGFβ1 mRNA in ROS17/2.8 cells and opposed the bFGF effect on TGFβ1 mRNA. bFGF also increased the steady-state level of TGFβ1 mRNA in mouse calvaria-derived MC3T3E1 and human osteosarcoma SaOS-2 cells. These findings indicate that FGF enhances the expression of TGFβ1 gene in osteoblast-like cells and point to the tight relationship of the two growth factors involved in the control of cellular functions.