Post-transcriptional stimulation of transforming growth factor β1 mRNA by TGF-β1 treatment of transformed human osteoblasts

Abstract

Following exogenous administration of transforming growth factor-beta 1 (TGF-beta 1) polypeptide to the human osteosarcoma cell line TE-85, we observed a 2- to 6-fold stimulation of steady-state TGF-beta 1 mRNA. The stimulation was dose- and time-dependent, as judged from Northern blot hybridization analyses. A 2- to 6-fold increase of the TGF-beta 1 polypeptide was also found in the media of these cells after TGF-beta 1 treatments. The autostimulation of TGF-beta 1 mRNA was nullified by cycloheximide treatment of the cells. The in vitro transcription rates of the TGF-beta 1 gene by isolated nuclei were not altered by TGF-beta 1 treatment. Under conditions of transcriptional inhibition, the stability of TGF-beta 1 mRNA was enhanced nearly two-fold by TGF-beta 1 treatment. Our findings indicate that TGF-beta 1 can stimulate autologous gene expression and subsequent polypeptide translation by a post-transcriptional mechanism requiring protein synthesis in human osteoblast-like cells. The recognized versatility of TGF-beta 1 autostimulation mechanisms (transcriptional and post-transcriptional) in other mesenchymal cells may apply also to skeletal cells, further underscoring the broad and potent activities of this cytokine.