Efficacy of ex vivo OPG gene therapy in preventing wear debris induced osteolysis
Aseptic loosening of prosthetic implants remains a serious orthopaedic problem and the greatest limitation to total joint arthroplasty. Central to the etiology of aseptic loosening is periprosthetic osteolysis at the bone–implant interface, which is caused by wear debris-induced inflammation. This i...
Saved in:
Published in | Journal of orthopaedic research Vol. 20; no. 2; pp. 169 - 173 |
---|---|
Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Elsevier Ltd
01.03.2002
Wiley Subscription Services, Inc., A Wiley Company Blackwell Publishing Ltd |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Aseptic loosening of prosthetic implants remains a serious orthopaedic problem and the greatest limitation to total joint arthroplasty. Central to the etiology of aseptic loosening is periprosthetic osteolysis at the bone–implant interface, which is caused by wear debris-induced inflammation. This inflammation produces the critical osteoclast differentiation factor RANKL, which directly stimulates osteoclastogenesis and osteoclastic bone resorption. A dominant factor known to counteract this process is the natural RANKL receptor antagonist protein OPG. Here we explore the potential of ex vivo OPG gene therapy for aseptic loosening by evaluating the efficacy of stably transfected fibroblast-like synoviocytes (FLS) expressing OPG in preventing wear debris-induced osteoclastogenesis, in a mouse calvaria model. Although the stably transfected fibroblasts produced small amounts of OPG (0.3 ng/ml/72 h/10
6 cells), this protein was very effective in preventing osteoclastic resorption as determined in a bone wafer assay. More importantly, implantation of 10
7 FLS–OPG, together with 30 mg of Ti wear debris, onto the calvaria of mice, completely inhibited osteoclastogenesis 3 days after surgery. Animals given FLS–LacZ control cells, which persisted for 3 days as determined by X-gal staining, together with the Ti particles, had a 6-fold increase in osteoclastogenesis compared to controls without Ti. This increased osteoclastogenesis was completely inhibited by the FLS–OPG, as osteoclast numbers in the calvaria of these animals were similar to that seen in the SHAM controls. |
---|---|
Bibliography: | PHS - No. AR45971; No. AR46545 OREF ark:/67375/WNG-M0537SDM-M ArticleID:JOR1100200202 istex:938E3831BBF3BDB23E59C7ACB34475700D51E844 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0736-0266 1554-527X |
DOI: | 10.1016/S0736-0266(01)00083-3 |