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

L. Zhang, T. H. Jia, A. C.M. Chong, L. Bai, H. Yu, W. Gong, P. H. Wooley, S. Y. Yang

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Exogenous osteoprotegerin (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 killing. Biomechanical pullout test indicated a significant restoration of implant stability after the cell-based OPG gene therapy. Histology revealed that inflammatory pseudo-membranes existed ubiquitously at bone-implant interface in control groups, whereas only observed sporadically in OPG gene-modified groups. Tartrate-resistant acid phosphataseosteoclasts and tumor necrosis factor α, interleukin-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.

Original languageEnglish (US)
Pages (from-to)1262-1269
Number of pages8
JournalGene Therapy
Volume17
Issue number10
DOIs
StatePublished - Oct 1 2010

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Keywords

  • aseptic loosening
  • cell-based therapy
  • implant stability
  • osteoprotegerin
  • periprosthetic osteolysis

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Zhang, L., Jia, T. H., Chong, A. C. M., Bai, L., Yu, H., Gong, W., Wooley, P. H., & Yang, S. Y. (2010). Cell-based osteoprotegerin therapy for debris-induced aseptic prosthetic loosening on a murine model. Gene Therapy, 17(10), 1262-1269. https://doi.org/10.1038/gt.2010.64