Effects of bone associated growth factors on DNA, collagen and osteocalcin synthesis in cultured fetal rat calvariae.
Studies in bone and bone cell cultures have shown that osteocalcin synthesis is dependent on the maturity of the osteoblast and the presence of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3. The bone matrix is a rich source of growth factors that play a role in bone formation, but their effects on osteocalcin synthesis and their interactions with 1,25(OH)2D3 have not been examined. Insulin-like growth factor I (IGF I), basic and acidic fibroblast growth factor (bFGF and aFGF), platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF beta), are growth factors associated with the bone matrix. These factors were shown to stimulate [3H]thymidine incorporation into DNA in 24 h cultures of fetal rat calvariae, and their effect was not modified by 1,25(OH)2D3. IGF I and TGF beta stimulated [3H]proline incorporation into calvarial collagen while the other growth factors studied did not; 1,25(OH)2D3 inhibited collagen synthesis in control as well as in IGF I and TGF beta treated calvariae. IGF I, bFGF and aFGF stimulated osteocalcin synthesis 1.5 to 2.5 fold but only IGF I was synergistic with the stimulatory effect of 1,25(OH)2D3. PDGF and TGF beta had no effect on osteocalcin synthesis. In conclusion, bone matrix-associated factors have important mitogenic effects in bone cultures, but only IGF I and FGFs stimulate osteocalcin synthesis, an effect that is of small magnitude when compared to that of 1,25(OH)2D3.
Canalis
E
E
Department of Medicine (Endocrine Section), St. Francis Hospital and Medical Center, Hartford 06105.
Lian
J B
JB
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000096:biosynthesis*; D003094:Collagen / Q000096:biosynthesis*; D046508:Culture Techniques; D004247:DNA / Q000096:biosynthesis*; D005333:Fetus; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D006133:Growth Substances / Q000378:metabolism / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II; D015675:Osteocalcin; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011506:Proteins / Q000494:pharmacology; D051381:Rats; D012886:Skull; D015291:Transforming Growth Factors / Q000494:pharmacology
D002135:Calcium-Binding Proteins; D006133:Growth Substances; C035170:IGF2 protein, human; D010982:Platelet-Derived Growth Factor; D011506:Proteins; D015675:Osteocalcin; D005346:Fibroblast Growth Factors; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D015291:Transforming Growth Factors; D003094:Collagen; D004247:DNA