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dc.contributor.authorZhang, L.
dc.contributor.authorJia, Tanghong
dc.contributor.authorChong, A.C.
dc.contributor.authorBai, Ling
dc.contributor.authorYu, Haiying
dc.contributor.authorGong, Weiming
dc.contributor.authorWooley, Paul H.
dc.contributor.authorYang, Shang-You
dc.identifier.citationL Zhang, T-H Jia, A C M Chong, L Bai, H Yu, W Gong, P H Wooley and S-Y Yang; Cell-based osteoprotegerin therapy for debris-induced aseptic prosthetic loosening on a murine model; Gene Therapy Oct.2010, V.17, No.10; P.1262-1269en_US
dc.identifier.issn1476-5462 (Electronic)
dc.identifier.issn0969-7128 (Linking)
dc.descriptionClick on the DOI link to access the publishers version of this article (may not be free) or click on the URI link to access the pre-print version. PMC2914841en_US
dc.description.abstractExogenous 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.en_US
dc.publisherNature Publishing Groupen_US
dc.relation.ispartofseriesGene Therapy;
dc.relation.ispartofseries;V.17, No.10
dc.subjectAseptic looseningen_US
dc.subjectPeriprosthetic osteolysisen_US
dc.subjectCell-based therapyen_US
dc.subjectImplant stabilityen_US
dc.titleCell-based osteoprotegerin therapy for debris-induced aseptic prosthetic loosening on a murine modelen_US

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