Gene transfer and expression of platelet-derived growth factors modulate periodontal cellular activity

Platelet-derived growth factor (PDGF) is a potent stimulator of wound heali ng. PDGF gene therapy may promote greater periodontal regeneration than loc al protein application, due to sustained growth factor delivery to the targ et tissue. This investigation tested the ability of recombinant adenoviruse s (rAds) encoding PDGF-A or PDGF-1308 (a PDGF-A dominant-negative mutant th at disrupts endogenous PDGF bioactivity) to affect cells derived from the p eriodontium. Osteoblasts, periodontal ligament fibroblasts, and gingival fi broblasts were transduced with rAds, and gene expression, DNA synthesis, an d cell proliferation were evaluated. The results revealed strong message fo r the PDGF-A gene for 7 days following gene delivery. Ad2/PDGF-A enhanced t he mitogenic and proliferative response in all cell types, while Ad2/PDGF-1 308 potently inhibited mitogenesis and proliferation. In conclusion, Ad2/PD GF can effectively transduce cells derived from the periodontium and promot e biological activity equivalent to PDGF-AA. These studies support the pote ntial use of gene therapy for sustained PDGF release in periodontal tissues .