Effects of bone associated growth factors on dna, collagen and osteocalcin synthesis in cultured fetal rat calvariae

Abstract

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 D 3 (1,25(OH) 2D 3. 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) 2D 3 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 β (TGFβ), 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) 2D 3. IGF I and TGFβ stimulated [ 3H]proline incorporation into calvarial collagen while the other growth factors studied did not; 1,25(OH) 2D 3 inhibited collagen synthesis in control as well as in IGF I and TGFβ 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) 2D 3. PDGF and TGFβ 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) 2D 3.