The effects of a sonicated Porphyromonas gingivalis ATCC 33277 protein extract on the mitogenic and chemotactic responses of human periodontal ligament (PDL) cells to the recombinant human platelet-derived growth factor-BB homodimer (PDGF-BB) were examined in vitro. Proliferation of PDL cells was inhibited by P. gingivalis extract at concentrations higher than 10 micrograms/mL protein. At 100 micrograms/mL of P. gingivalis extract, cells did not proliferate. DNA synthesis in PDL cells, as revealed by [3H]-thymidine incorporation, was also inhibited by approximately 50% in the presence of 50 micrograms/mL P. gingivalis extract for 24 hours. In contrast, PDGF-BB at 1 ng/mL enhanced DNA synthesis in PDL cells, followed by maximum enhancement at concentrations higher than 10 ng/mL PDGF-BB. However, this mitogenic response to PDGF-BB was markedly reduced in the presence of 20 micrograms/mL of P. gingivalis extract and did not reach the maximum level even if PDGF-BB concentrations were increased to 250 ng/mL. PDL cells exhibited a chemotactic response to PDGF-BB at 1 ng/mL, which was also inhibited by pretreatment of the cells with P. gingivalis extract at 10 to 50 micrograms/mL. Scatchard analysis of a [125I]-PDGF binding assay demonstrated that PDL cells have both high and low PDGF binding affinity sites. Treatment of the cells with P. gingivalis extract decreased the number of PDGF-binding sites to approximately 35% of the control level, while it caused only a slight change in the affinities of both types of binding site. These results indicated that the P. gingivalis extract reduced mitogenic and chemotactic responses of human PDL cells, possibly through mechanisms involving a decrease in PDGF-binding capacity of these cells. Due to this inhibitory effect of P. gingivalis, the normal levels of PDGF in periodontal lesions may not be sufficient to promote periodontal regeneration through activation of PDL cell proliferation and migration. Therefore, the therapeutic use of PDGF-BB, as a supplement to pre-existing PDGF and as an adjunct, while also eliminating P. gingivalis from periodontal lesions, would help periodontal tissue regeneration.