Effects of insulin-like growth factor (IGF) binding proteins (BPs) -3 and -6 on DNA synthesis of rat osteoblasts: further evidence for a role of auto-/paracrine IGF I but not IGF II in stimulating osteoblast growth.
IGFBP-3 and IGFBP-6 were used to study whether both IGF I and IGF II play a role in auto-/paracrine stimulation of rat osteoblast growth. Both IGFBPs decreased basal DNA synthesis in neonatal rat calvaria cells but with different potencies. Consistent with their IGF binding affinities, IGFBP-3 blocked both IGF I- and IGF II-stimulated DNA synthesis, whereas IGFBP-6 preferentially blocked IGF II-stimulated DNA synthesis. These inhibitory effects of the two IGFBPs can be fully explained by the sequestration of IGFs. Because IGFBP-6 preferentially binds IGF II and is much less potent than IGFBP-3 in decreasing basal DNA synthesis in calvaria cells, IGF I but not IGF II appears to be an important auto-/paracrine stimulator of DNA synthesis.
Schmid
C
C
Dept. of Medicine, University Hospital, Zürich, Switzerland.
Schläpfer
I
I
Keller
A
A
Waldvogel
M
M
Froesch
E R
ER
Zapf
J
J
D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis* / Q000187:drug effects; D006801:Humans; D018976:Insulin-Like Growth Factor Binding Protein 6; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D007700:Kinetics; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D012886:Skull; D013936:Thymidine / Q000378:metabolism
D002352:Carrier Proteins; D018976:Insulin-Like Growth Factor Binding Protein 6; D018969:Insulin-Like Growth Factor Binding Proteins; D011994:Recombinant Proteins; C094553:insulin-like growth factor I, Gln(3)-Ala(4)-Tyr(15)-Leu(16)-; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D004247:DNA; D013936:Thymidine