Carboxy-truncated insulin-like growth factor binding protein-5 stimulates mitogenesis in osteoblast-like cells.
Recently we demonstrated that a 23 kDa form of IGFBP-5, derived from osteoblast-like cells, stimulates osteoblast mitogenesis and enhances IGF-I action. Because osteoblast-derived IGFBP-5 is smaller than recombinant intact IGFBP-5 (23 vs 30 kDa) and has decreased binding affinity for IGF-I, we proposed that the native 23 kDa form of IGFBP-5 was truncated at a carboxy-terminal position. We now show that a recombinant form of carboxy-truncated IGFBP-5 binds IGF-I with reduced affinity and stimulates mitogenesis in mouse osteoblasts. We also show that 125I-truncated IGFBP-5 specifically binds to osteoblast monolayers with low binding affinity, similar to that seen with native 23 kDa IGFBP-5. These data indicate that carboxy-truncated IGFBP-5 stimulates osteoblast mitogenesis and suggest that reduced IGF-binding and cell-surface attachment are local mediators of this response.
Andress
D L
DL
Research Service, Veterans Affairs Medical Centers, Seattle, Washington 98108.
Loop
S M
SM
Zapf
J
J
Kiefer
M C
MC
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D001842:Bone and Bones / Q000166:cytology; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D018975:Insulin-Like Growth Factor Binding Protein 5; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008934:Mitogens / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects; D012516:Osteosarcoma; D016133:Polymerase Chain Reaction / Q000379:methods; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D018975:Insulin-Like Growth Factor Binding Protein 5; D008934:Mitogens; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D013936:Thymidine