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.
Canalis
E
E
Department of Research, Saint Francis Hospital, Hartford, Connecticut, USA.
Gabbitas
B
B
D000818:Animals; D001483:Base Sequence; D001842:Bone and Bones / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D017931:DNA Primers / Q000737:chemistry; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D015870:Gene Expression; D006918:Hydroxyurea / Q000494:pharmacology; D018975:Insulin-Like Growth Factor Binding Protein 5; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D012332:RNA, Heterogeneous Nuclear / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013002:Somatomedins; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D002352:Carrier Proteins; D017931:DNA Primers; D018975:Insulin-Like Growth Factor Binding Protein 5; D010982:Platelet-Derived Growth Factor; D012332:RNA, Heterogeneous Nuclear; D012333:RNA, Messenger; D013002:Somatomedins; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D003513:Cycloheximide; D006918:Hydroxyurea