Platelet-derived growth factor enhances deoxyribonucleic acid and collagen synthesis in osteoblast-enriched cultures from fetal rat parietal bone.
Platelet-derived growth factor (PDGF) or closely related proteins are found in bone matrix and are produced by cultured osteosarcoma cells. In serum-deprived osteoblast-enriched (ob) cultures from fetal rat bone, recombinant human PDGF (composed of a B chain homodimer) at 0.1-3 nM enhanced the rate of DNA synthesis by 2- to 8-fold within 24 h of treatment, and 0.3-3 nM PDGF increased cell number by 1.3- to 1.6-fold. Unlike results with rat kidney fibroblast cultures, the mitogenic effect of PDGF in ob cultures was not synergistic with that of insulin-like growth factor I. PDGF at 0.3-10 nM also enhanced the rates of collagen and noncollagen protein synthesis in ob cultures by 1.5- to 4.0-fold, and these increases were blocked when DNA synthesis was prevented. The stimulatory effects of PDGF did not appear specific to ob cultures from fetal rat bone, since similar increases were found in bone cell cultures containing fibroblasts and osteoblast precursors. PDGF binding at 4 C to ob cultures indicated a single class of receptors with a Kd of 0.16 nM and approximately 60,000 sites/cell. Polyacrylamide gel of 125I-PDGF bound and cross-linked to ob cultures revealed a single radioactive band at approximately 180,000-190,000 mol wt. The present studies, therefore, indicate that PDGF can directly increase replication and matrix protein synthesis by both differentiated and undifferentiated bone cells, and that bone- or platelet-derived PDGF may have an important anabolic role in bone remodeling or fracture repair.
Centrella
M
M
Department of Medicine (Endocrine Section), Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105.
McCarthy
T L
TL
Canalis
E
E
D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D004247:DNA / Q000096:biosynthesis*; D005333:Fetus / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008934:Mitogens / Q000494:pharmacology; D009994:Osmolar Concentration; D010006:Osteoblasts / Q000378:metabolism*; D010294:Parietal Bone / Q000166:cytology / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D014176:Protein Biosynthesis; D051381:Rats
D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D004247:DNA