Gene transfer and expression of platelet-derived growth factors modulate periodontal cellular activity.
Platelet-derived growth factor (PDGF) is a potent stimulator of wound healing. PDGF gene therapy may promote greater periodontal regeneration than local protein application, due to sustained growth factor delivery to the target tissue. This investigation tested the ability of recombinant adenoviruses (rAds) encoding PDGF-A or PDGF-1308 (a PDGF-A dominant-negative mutant that disrupts endogenous PDGF bioactivity) to affect cells derived from the periodontium. Osteoblasts, periodontal ligament fibroblasts, and gingival fibroblasts were transduced with rAds, and gene expression, DNA synthesis, and cell proliferation were evaluated. The results revealed strong message for the PDGF-A gene for 7 days following gene delivery. Ad2/PDGF-A enhanced the mitogenic and proliferative response in all cell types, while Ad2/PDGF-1308 potently inhibited mitogenesis and proliferation. In conclusion, Ad2/PDGF can effectively transduce cells derived from the periodontium and promote biological activity equivalent to PDGF-AA. These studies support the potential use of gene therapy for sustained PDGF release in periodontal tissues.
Zhu
Z
Z
Dept. of Microbiology and Molecular Genetics, Harvard Medical School & Dana-Farber/Harvard Cancer Center, Boston, MA, USA.
Lee
C S
CS
Tejeda
K M
KM
Giannobile
W V
WV
D000256:Adenoviridae / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division / Q000235:genetics; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D009154:Mutation / Q000235:genetics; D010006:Osteoblasts / Q000378:metabolism; D010513:Periodontal Ligament / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D010957:Plasmids; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D012038:Regeneration; D013223:Statistics as Topic; D014161:Transduction, Genetic; D014162:Transfection; D014945:Wound Healing
D010982:Platelet-Derived Growth Factor; C075278:platelet-derived growth factor A; D004247:DNA