Differential effects of platelet-derived growth factor isoforms on plasminogen activator activity in fetal rat osteoblasts due to isoform-specific receptor functions.
We examined receptor binding and metabolic effects of the platelet-derived growth factor (PDGF) isoforms AA, AB, and BB in cultures of osteoblastic cells from fetal rat calvaria. Saturation binding experiments demonstrated the presence of 6,000 binding sites for PDGF-AA, 42,000 for PDGF-AB, and 60,000 for PDGF-BB. Binding competition experiments were compatible with the recently postulated model of three PDGF receptor subtypes with differential affinity for the PDGF isoforms. The effects of the PDGF isoforms on DNA synthesis, collagen synthesis, and alkaline phosphatase activity in osteoblasts strictly correlated with the number of available binding sites. Accordingly, PDGF-BB was the most potent isoform, PDGF-AB was slightly less potent, and PDGF-AA was the least potent. In contrast, we found that PDGF-BB was less potent than PDGF-AB in increasing plasminogen activator activity in the osteoblast-conditioned medium. Our data strongly suggest that the PDGF receptor subtypes in fetal rat osteoblasts not only selectively bind one or more PDGF isoforms, but are also capable of responding differently to these isoforms.
Pfeilschifter
J
J
Department of Internal Medicine I, University of Heidelberg, Germany.
Krempien
R
R
Naumann
A
A
Gronwald
R G
RG
Hoppe
J
J
Ziegler
R
R
D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D005260:Female; D005333:Fetus / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010960:Plasminogen Activators / Q000032:analysis*; D015849:Plasminogen Inactivators / Q000032:analysis; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D011956:Receptors, Cell Surface / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D017479:Receptors, Platelet-Derived Growth Factor
D015849:Plasminogen Inactivators; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D003094:Collagen; D004247:DNA; D017479:Receptors, Platelet-Derived Growth Factor; D000469:Alkaline Phosphatase; D010960:Plasminogen Activators