SKELETAL GROWTH-FACTORS REGULATE THE SYNTHESIS OF INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-5 IN BONE CELL-CULTURES

Skeletal cells secrete insulin-like growth factors (IGFs) I and II and six known IGF binding proteins (IGFBPs). IGFBP-5 stimulates bone formation, and its synthesis correlates with changes in osteoblast cell growth. We tested the effects of basic fibroblast growth factor (bFGF), transforming growth factor beta 1 (TGF beta 1), and platelet derived growth factor (PDGF) BB on IGFBP-5 expression in cultures of osteoblast-enriched cells from 22 day-old fetal rat calvariae (Ob cells). Treatment of Ob cells with bFGF, TGF beta 1, and PDGF BB caused a time- and dose dependent decrease in IGFBP-5 mRNA levels and inhibited IGFBP-5 polypeptide levels in the extracellular matrix. The effects of bFGF, TGF beta 1, and PDGF BB on IGFBP-5 transcripts were independent of cell division and were observed in the presence and absence of hydroxyurea. bFGF, TGF beta 1, and PDGF BB did not modify the decay of IGFBP-5 mRNA in transcriptionally arrested Ob cells, and they inhibited IGFBP-5 heterogeneous nuclear RNA and the rate of IGFBP-5 transcription. In conclusion, bFGF, TGF beta 1, and PDGF BB inhibit IGFBP-5 expression in Ob cells independently of their mitogenic activity and through mechanisms that involve decreased transcription.