Effects and fate of human IGF-binding protein-5 in rat osteoblast cultures.
Osteoblasts prepared from calvaria of newborn rats produce insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP), IGFBP-5 was discovered in bone extracts. However, we could not detect IGFBP-5 in the medium of newborn rat osteoblasts, although we found mRNA expression. To find an explanation for this discrepancy and to learn more about the physiological role of IGFBP-5 in these cells, we studied the biological activity and the fate of recombinant human (rh) IGFBP-5 in comparison to rhIGFBP-3. IGFBP-5 but not IGFBP-3 stimulated thymidine incorporation into DNA both in the absence and presence of IGF-I. However, IGFBP-5 did not enhance uridine incorporation into RNA and glucose incorporation into glycogen. 125I-rhIGFBP-5 but not 125I-rhIGFBP-3 rapidly disappeared from the culture medium consistent with the observation that endogenous (rat) IGFBP-3 but not IGFBP-5 accumulated in the medium. However, intact 125I-labeled or unlabeled rhIGFBP-5 was associated with the cell-layer matrix, whereas IGFBP-5 fragments appeared in the medium. Trapping of IGFBP-5 in the cell layer matrix may enhance local availability of IGF.
Schmid
C
C
Department of Internal Medicine, University Hospital, Zürich, Switzerland.
Schläpfer
I
I
Gosteli-Peter
M A
MA
Froesch
E R
ER
Zapf
J
J
D000818:Animals; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects*; D006003:Glycogen / Q000096:biosynthesis*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000494:pharmacology; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000378:metabolism / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D012313:RNA / Q000096:biosynthesis* / Q000187:drug effects; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology
D018972:Insulin-Like Growth Factor Binding Protein 3; D018975:Insulin-Like Growth Factor Binding Protein 5; D011994:Recombinant Proteins; D012313:RNA; D006003:Glycogen