Insulin-like growth factors sustain insulin-like growth factor-binding protein-5 expression in osteoblasts.
Insulin-like growth factors (IGFs) I and II are considered to be autocrine regulators of bone cell function. Recently, we demonstrated that IGF-I induces IGF-binding protein-5 (IGFBP-5) expression in cultures of osteoblast-enriched cells from 22-day fetal rat calvariae (Ob cells). In the present study, we postulated that IGFs play an autocrine role in the maintenance of IGFBP-5 basal expression in Ob cells. IGFBP-2 and -3, at concentrations that bind endogenous IGFs, decreased IGFBP-5 mRNA levels, as determined by Northern blot analysis, and protein levels, as determined by Western immunoblots of extracellular matrix extracts of Ob cells. IGFBP-2 and -3 in excess inhibited IGFBP-5 heterogeneous nuclear RNA levels, as determined by RT-PCR, and did not alter the half-life of IGFBP-5 mRNA in transcriptionally arrested Ob cells. In conclusion, blocking endogenous IGFs in Ob cells represses IGFBP-5 expression, suggesting that IGFs are autocrine inducers of IGFBP-5 synthesis in osteoblasts.
Departments of Research and Medicine, Saint Francis Hospital and Medical Center, Hartford, CT 06105, USA.
B
B
Gabbitas
E
E
Canalis
D000818:Animals; D002478:Cells, Cultured; D005333:Fetus; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000502:physiology; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000502:physiology; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000096:biosynthesis* / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology* / Q000502:physiology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology* / Q000502:physiology; D007700:Kinetics; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D012886:Skull; D014158:Transcription, Genetic / Q000187:drug effects
D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018975:Insulin-Like Growth Factor Binding Protein 5; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II