Recombinant human [Cys281]insulin-like growth factor-binding protein 2 inhibits both basal and insulin-like growth factor I-stimulated proliferation and collagen synthesis in fetal rat calvariae.
It is recognized that insulin-like growth factors (IGFs) are bound to specific high-affinity insulin-like growth factor-binding proteins (IGFBPs). The role of IGFBPs in bone metabolism is not well established. The effect of recombinant human [Cys281]IGFBP-2 ([Cys281]rhIGFBP-2) on bone formation in 21-day-old fetal rat calvariae was investigated. [Cys281]rhIGFBP-2 was expressed in and purified from conditioned medium of a clonal Chinese hamster ovary cell line. IGF-I-stimulated cell proliferation was inhibited dose dependently by [Cys281]rhIGFBP-2, with half-maximal inhibition observed at 2 x 10(-8) M. Suppression of the IGF-I-stimulated DNA synthesis was observed at an apparent dose ratio of 1:10. [Cys281]rhIGFBP-2 (10(-6) M) also inhibited the basal incorporation of [3H]thymidine into DNA by up to 45%. Insulin-stimulated cell proliferation was not affected in the presence of the binding protein. In addition, [Cys281]rhIGFBP-2 inhibited bone collagen synthesis under basal and IGF-I-stimulated conditions. In contrast, [Cys281]rhIGFBP-2 did not alter the parathyroid hormone-stimulated bone cell proliferation rate. In conclusion, binding of hIGF-I to rhIGFBP-2 results in an inhibition of the actions of free IGF-I on bone cell replication and matrix synthesis. Parathyroid hormone-stimulated cell proliferation is not mediated by an increase in free IGFs.
Feyen
J H
JH
Department of Endocrinology, Sandoz Pharma Limited, Basel, Switzerland.
Evans
D B
DB
Binkert
C
C
Heinrich
G F
GF
Geisse
S
S
Kocher
H P
HP
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D003094:Collagen / Q000096:biosynthesis*; D006224:Cricetinae; D003412:Cricetulus; D003545:Cysteine / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D006909:Hydroxyproline / Q000032:analysis; D018974:Insulin-Like Growth Factor Binding Protein 4; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009154:Mutation; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D012886:Skull / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism
D002352:Carrier Proteins; D018974:Insulin-Like Growth Factor Binding Protein 4; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D004247:DNA; D003545:Cysteine; D006909:Hydroxyproline; D013936:Thymidine