Adenoviral vector-mediated overexpression of osteoprotegerin accelerates osteointegration of titanium implants in ovariectomized rats.

This study investigated the efficacy of human osteoprotegerin (hOPG) transgene to accelerate osteointegration of titanium implant in ovariectomized (OVX) rats. Bone marrow stromal cells transduced with Ad-hOPG-EGFP could sustainedly express hOPG. Osteoclast precursor RAW264.7 cells treated by the hOPG were examined by tartrate-resistant acid phosphatase (TRAP) staining and bone slice resorption assay. The results showed differentiation and function of osteoclasts were significantly suppressed by hOPG in vitro. Ad-hOPG-EGFP was locally administered to the bone defect prior to implant placement in OVX and sham rats. After 3, 7, 28 days of implantation, the femurs were harvested for molecular and histological analyses. Successful transgene expression was confirmed by western blot and cryosectioning. A significant reduction in TRAP+ numbers was detected in Ad-hOPG-EGFP group. Real-time reverse transcriptase-PCR examination revealed that hOPG transgene markedly diminished the expression of cathepsin K and receptor activator for nuclear factor-κ B ligand in vivo. The transgene hOPG modification revealed a marked increasing osteointegration and restored implant stability in OVX rats (P<0.01), compared with the control groups (Ad-EGFP or sterilized phosphate-buffered saline) 28 days after implantation. In conclusion, hOPG via direct adenovirus-mediated gene transfer could accelerate osteointegration of titanium implants in OVX rats. Osteoprotegerin gene therapy may be an effective strategy to osteointegration of implants under osteoporotic conditions.