E. Canalis et B. Gabbitas, SKELETAL GROWTH-FACTORS REGULATE THE SYNTHESIS OF INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-5 IN BONE CELL-CULTURES, The Journal of biological chemistry, 270(18), 1995, pp. 10771-10776
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.