POSTTRANSCRIPTIONAL STIMULATION OF TRANSFORMING GROWTH-FACTOR-BETA-1 MESSENGER-RNA BY TGF-BETA-1 TREATMENT OF TRANSFORMED HUMAN OSTEOBLASTS

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-bet a 1 treatments, The autostimulation of TGF-beta 1 mRNA was nullified b y cycloheximide treatment of the cells. The in vitro transcription rat es of the TGF-beta 1 gene by isolated nuclei were not altered by TGF-b eta 1 treatment. Under conditions of transcriptional inhibition, the s tability of TGF-beta 1 mRNA was enhanced nearly two-fold by TGF-beta 1 treatment. Our findings indicate that TGF-beta 1 can stimulate autolo gous gene expression and subsequent polypeptide translation by a post- transcriptional mechanism requiring protein synthesis in human osteobl ast-like cells. The recognized versatility of TGF-beta 1 autostimulati on mechanisms (transcriptional and post-transcriptional) in other mese nchymal cells may apply also to skeletal cells, further underscoring t he broad and potent activities of this cytokine.