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 form ation, and its synthesis correlates with changes in osteoblast cell gr owth. We tested the effects of basic fibroblast growth factor (bFGF), transforming growth factor beta 1 (TGF beta 1), and platelet derived g rowth factor (PDGF) BB on IGFBP-5 expression in cultures of osteoblast -enriched cells from 22 day-old fetal rat calvariae (Ob cells). Treatm ent 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 p olypeptide levels in the extracellular matrix. The effects of bFGF, TG F 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 mRN A in transcriptionally arrested Ob cells, and they inhibited IGFBP-5 h eterogeneous nuclear RNA and the rate of IGFBP-5 transcription. In con clusion, bFGF, TGF beta 1, and PDGF BB inhibit IGFBP-5 expression in O b cells independently of their mitogenic activity and through mechanis ms that involve decreased transcription.