title: 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 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.
authors.affiliation: Department of Medicine (Endocrine Section), St. Francis Hospital and Medical Center, Hartford 06105.
authors.forename: E
authors.initials: E
authors.lastname: Canalis
authors.forename: J B
authors.initials: JB
authors.lastname: Lian
mesh_terms: 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
chemical_list: 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