Characterization, regulation, and function of specific cell membrane receptors for insulin-like growth factor I on bone endothelial cells.
It is now widely accepted that insulin-like growth factor-I (IGF-I) has a local regulatory role in bone remodeling. IGF-I has also been demonstrated to regulate proliferation of bone-derived endothelial cells. Such studies suggest a role of IGF-I in skeletal angiogenesis. Using BBE cells, a bovine bone endothelial cell line, we characterized the kinetics and chemical properties of IGF-I receptors and examined the effect of IGF-I on bone endothelium migration. Two classes of binding sites with high affinity for IGF-I were detected by binding experiments on bone endothelial cells. Both competition analyses and cross-linking studies revealed the presence of type I IGF receptor in bone endothelial cells. Moreover, these cells produced and released authentic IGF-I into the medium, as evidenced by radioimmunoassay analyses of gel-filtered conditioned media. Both IGF-I binding capacity and release decreased either with increases in cell number or after treatment with 17 beta-estradiol (17 beta E2) and parathyroid hormone (PTH). Both hormones also inhibited chemotactic responses of bone endothelial cells to IGF-I. Taken together, these results strongly suggest that IGF-I, a growth factor that promotes the proliferation of various bone cell types, also induces growth and chemotactic responses in bone endothelium acting through the type I IGF receptor. This may be part of a generalized response of bone cells to IGF-I that facilitates cell migration.
Fiorelli
G
G
Department of Clinical Physiopathology, University of Florence, Italy.
Orlando
C
C
Benvenuti
S
S
Franceschelli
F
F
Bianchi
S
S
Pioli
P
P
Tanini
A
A
Serio
M
M
Bartucci
F
F
Brandi
M L
ML
D000704:Analysis of Variance; D000818:Animals; D001667:Binding, Competitive; D001842:Bone and Bones / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects; D002850:Chromatography, Gel; D004727:Endothelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D010281:Parathyroid Hormone / Q000494:pharmacology; D011863:Radioimmunoassay; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology
D010281:Parathyroid Hormone; D011994:Recombinant Proteins; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1