Insulin-like growth factor I has independent effects on bone matrix formation and cell replication.
The effects of insulin-like growth factor-I (IGF-I) and insulin on bone matrix synthesis and bone cell replication were studied in cultured 21-day-old fetal rat calvariae. Histomorphometry techniques were developed to measure the incorporation of [2,3-3H]proline and [methyl-3H]thymidine into bone matrix and bone cell nuclei, respectively, using autoradiographs of sagittal sections of calvariae cultured with IGF-I, insulin, or vehicle for up to 96 h. To confirm an effect on bone formation, IGF-I was also studied for its effects on [3H]proline incorporation into collagenase-digestible protein (CDP) and noncollagen protein and on [3H]thymidine incorporation into acid-precipitable material (DNA). IGF-I at 10(-9)-10(-7) M significantly increased the rate of bone matrix apposition and CDP after 24 h by 45-50% and increased cell labeling by 8-fold in the osteoprogenitor cell zone, by 4-fold in the osteoblast cell zone, and by 2-fold in the periosteal fibroblast zone. Insulin at 10(-9)-10(-6) M also increased matrix apposition rate and CDP by 40-50%, but increased cell labeling by 2-fold only at a concentration of 10(-7) M or higher and then only in the osteoprogenitor cell zone. When hydroxyurea was added to IGF-I-treated bones, the effects of IGF-I on DNA synthesis were abolished, but the increase in bone matrix apposition induced by IGF-I was only partly diminished. In conclusion, IGF-I stimulates matrix synthesis in calvariae, an effect that is partly, although not completely, dependent on its stimulatory effect on DNA synthesis.
Hock
J M
JM
Veterans Administration Medical Center, Newington, Connecticut 06111.
Centrella
M
M
Canalis
E
E
D000818:Animals; D001345:Autoradiography; D001857:Bone Matrix / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D001842:Bone and Bones / Q000166:cytology* / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects; D005333:Fetus; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D009924:Organ Culture Techniques; D010012:Osteogenesis / Q000187:drug effects*; D011392:Proline / Q000378:metabolism; D013002:Somatomedins / Q000494:pharmacology*; D014316:Tritium
D013002:Somatomedins; D014316:Tritium; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D011392:Proline