PULSE APPLICATION OF PLATELET-DERIVED GROWTH-FACTOR ENHANCES FORMATION OF A MINERALIZING MATRIX WHILE CONTINUOUS APPLICATION IS INHIBITORY

Platelet-derived growth factor (PDGF) stimulates chemotaxis and prolif eration of osteoblasts, and induces bone formation in vivo. To determi ne how PDGF might regulate these cells, the effect of PDGF on long-ter m mineralizing cultures of fetal rat osteoblastic cells was examined. Although PDGF increased cell proliferation in these cultures, continuo us treatment with PDGF caused a dose-dependent decrease in mineralized nodule formation. When cells were treated with multiple, brief (1 day ) exposures to PDGF at the osteoblast differentiation stage, there was a significant 50% increase in mineralized nodule area. Based on modul ation of alkaline phosphatase activity it appears that longer-term exp osure to PDGF reduces mineralized nodule formation largely by inhibiti ng differentiated osteoblast function, while short-term exposure enhan ces proliferation without inhibiting the differentiated phenotype. Thu s, the ultimate affect of PDGF on bone formation is likely to reflect two processes: a positive effect through enhancing cell number or a ne gative effect by inhibiting differentiated function. The inhibitory ef fect of PDGF on formation of a mineralized matrix is unlikely to be si mply a result of enhanced proliferation of ''fibroblastic'' cells sinc e cultures treated with PDGF for 3 days and then transferred to new pl astic dishes exhibited a 70% increase in mineralized nodule area compa red to controls. These results would predict that multiple, brief expo sures to PDGF would enhance bone formation in vivo, white prolonged ex posure to PDGF, which is likely to occur in chronic inflammation, woul d inhibit differentiated osteoblast function and limit bone regenerati on. (C) 1998 Wiley-Liss, Inc.