This study investigated the efficacy of human osteoprotegerin (hOPG) transgene to accelerate osteointegration of titanium implant\nin ovariectomized (OVX) rats. Bone marrow stromal cells transduced with Ad-hOPG-EGFP could sustainedly express hOPG.\nOsteoclast precursor RAW264.7 cells treated by the hOPG were examined by tartrate-resistant acid phosphatase (TRAP) staining and\nbone slice resorption assay. The results showed differentiation and function of osteoclasts were significantly suppressed by hOPG\nin vitro. Ad-hOPG-EGFP was locally administered to the bone defect prior to implant placement in OVX and sham rats. After 3, 7,\n28 days of implantation, the femurs were harvested for molecular and histological analyses. Successful transgene expression was\nconfirmed by western blot and cryosectioning. A significant reduction in TRAP+ numbers was detected in Ad-hOPG-EGFP group.\nReal-time reverse transcriptase-PCR examination revealed that hOPG transgene markedly diminished the expression of cathepsin K\nand receptor activator for nuclear factor-? B ligand in vivo. The transgene hOPG modification revealed a marked increasing\nosteointegration and restored implant stability in OVX rats (Po0.01), compared with the control groups (Ad-EGFP or sterilized\nphosphate-buffered saline) 28 days after implantation. In conclusion, hOPG via direct adenovirus-mediated gene transfer could\naccelerate osteointegration of titanium implants in OVX rats. Osteoprotegerin gene therapy may be an effective strategy to\nosteointegration of implants under osteoporotic conditions.
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