Platelet-derived growth factor stimulates bone resorption via a prostaglandin-mediated mechanism.
Platelet-derived growth factor (PDGF) stimulated up to 15-fold the production of prostaglandin E2 (PGE2) and bone resorption in neonatal mouse calvaria in organ culture. The action of PDGF on bone resorption occurred at low concentrations of the protein (ED50 = 10 ng/ml). All concentrations of PDGF which stimulated resorption also enhanced the production of PGE2 by bone; concentrations of PDGF which did not stimulate resorption did not enhance PGE2 production. PDGF-induced formation of PGE2 and bone resorption were inhibited completely by indomethacin (100 ng/ml) and hydrocortisone (1 microgram/ml). Indomethacin did not inhibit the bone resorption-stimulating activity of exogenous PGE2. In the continued presence of a maximum concentration of PDGF (100 ng/ml), an increase in bone resorption, as measured by an increase in medium calcium, was detected at 16 h (P less than 0.01), but not at 12 h; however, an increase in PGE2 production occurred within the first 2 h of treatment. A similar lag period for the onset of bone resorption was seen after the addition of exogenous PGE2 to the culture medium. On the other hand, exposure of bones to PDGF (50 ng/ml) for as brief a period as 5-15 min, followed by washout of PDGF, triggered bone resorption over the subsequent 48 h. PDGF increased cAMP production by bone within 30 min, and this effect of PDGF was blocked completely by indomethacin while the action of exogenous PGE2 on the production of cAMP was not blocked by indomethacin. The action of a low concentration of PDGF (1 ng/ml), which did not stimulate bone resorption alone, was potentiated by the phosphodiesterase inhibitor isobutylmethylxanthine (4 microM). We conclude that low concentrations of PDGF stimulate bone resorption via the enhanced local production of PGE2.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001862:Bone Resorption / Q000187:drug effects*; D002118:Calcium / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D009924:Organ Culture Techniques; D010455:Peptides / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor; D011458:Prostaglandins E / Q000096:biosynthesis / Q000494:pharmacology; D013997:Time Factors
D006133:Growth Substances; D010455:Peptides; D010982:Platelet-Derived Growth Factor; D011458:Prostaglandins E; D000242:Cyclic AMP; D015232:Dinoprostone; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine