Cell-based osteoprotegerin therapy for debris-induced aseptic prosthetic loosening on a murine model

Abstract

Exogenous OPG gene modification appears a therapeutic strategy for osteolytic aseptic loosening. The feasibility and efficacy of a cell-based OPG gene delivery approach were investigated using a murine model of knee prosthesis failure. A titanium pin was implanted into mouse proximal tibia to mimic a weight-bearing knee arthroplasty, followed by titanium-particles challenge to induce periprosthetic osteolysis. Mouse fibroblast-like synoviocytes were transduced in vitro with either AAV-OPG or AAV-LacZ before transfused into the osteolytic prosthetic joint 3 weeks post surgery. Successful transgene expression at the local site was confirmed 4 weeks later after sacrifice. Biomechanical pull-out test indicated a significant restoration of implant stability following the cell-based OPG gene therapy. Histology revealed that inflammatory pseudo-membranes existed ubiquitously at bone-implant interface in control groups, while only observed sporadically in OPG gene-modified groups. TRAP+ osteoclasts and TNFα, IL-1β, CD68+ expressing cells were significantly reduced in periprosthetic tissues of OPG gene-modified mice. No transgene dissemination or tumorigenesis was detected in remote organs and tissues. Data suggest that cell based ex vivo OPG gene therapy was comparable in efficacy with in vivo local gene transfer technique to deliver functional therapeutic OPG activities, effectively halted the debris-induced osteolysis and regained the implant stability in this model.

Intermittent Parathyroid Hormone Enhances Cancellous Osseointegration of a Novel Murine Tibial Implant

“…taken to minimize the amount of tissue removed and to not move the implant in the process 28 . The long axis of the implant was aligned with the axis of pullout loading.…”

“…The distal end was potted in polymethylmethacrylate. Bone at the proximal end was dissected with a number-11 scalpel blade to allow the clamp of a custom fixture 28 to hold the implant under its plateau. Care was Dimensions and use of the novel titanium tibial implant, which was manufactured with three-dimensional metal printing.…”

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

“…[15][16][17] Recombinant OPG was also a potent pharmacologic inhibitor of bone resorption. 18,19 Thus, hOPG might be an effective candidate to inhibit the bone remodeling.…”

Biology of implant wear

“…102 The feasibility and efficacy of a cell-based OPG gene delivery approach has been recently investigated using a murine model of prosthesis failure. 103 To mimic a weight-bearing knee arthroplasty, a titanium pin was implanted into mouse proximal tibia, followed by titanium particles challenge to induce periprosthetic osteolysis. Following in vitro transduction of mouse fibroblast-like synoviocytes with OPG, these cells were transfused in the osteolytic joint three weeks post-surgery.…”