Effects of platelet-derived growth factor isoforms on calcium release from neonatal mouse calvariae

Platelet-derived growth factor (PDGF) is the major growth factor in serum for cells of mesenchymal origin and induces many different activities, including bone resorption. Since the initial report that PDGF stimulated calcium release from bone organ cultures, it has been shown that PDGF is a dimeric protein consisting of two disulfide bonded polypeptides encoded by different genes. Three isoforms of the two gene products have been isolated. We compared the capacity of each isoform to stimulate calcium release from radiolabeled mouse calvariae. PDGF-AB from human platelets and recombinant PDGF-BB isoforms significantly stimulated calcium release at 5 ng/ml, but not in lower doses. Recombinant PDGF-AA did not induce calcium release. Indomethacin blocked the stimulated bone resorption, suggesting a prostaglandin-mediated mechanism of action. PDGF-induced calcium release was compared to TGF-beta 1 in the organ culture system. Approximately a 10-fold greater concentration of PDGF-AB and PDGF-BB was required to achieve a similar degree of calcium release as found in TGF-beta 1 treated calvariae. Thus, TGF-beta 1, PDGF-AB, and PDGF-BB significantly stimulated calcium release from mouse calvariae. This response is specific in that PDGF-AA did not stimulate calcium release.