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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 β1 (TGF β1), 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 β1, 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 β1, and PDGF BB on IGFBP-5 transcripts were independent of cell division and were observed in the presence and absence of hydroxyurea. bFGF, TGF β1, 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 β1, and PDGF BB inhibit IGFBP-5 expression in Ob cells independently of their mitogenic activity and through mechanisms that involve decreased transcription.