NFκB gene silencing inhibits wear particles-induced inflammatory osteolysis.pdf

Medical Hypotheses (2008) 71, 727–729 /locate/mehy NFjB gene silencing inhibits wear particles-induced inflammatory osteolysis Tao Cheng, Xianlong Zhang * Department of Orthopaedic Surgery, Shanghai Sixth People’s Hospital, Medical College, Shanghai Jiaotong University, Shanghai 200233, PR China Received 28 June 2008; revised 28 June 2008; accepted 2 July 2008 Summary Wear particles-induced periprosthetic osteolysis involved in proinflammatory cytokine production and osteoclastogenesis, is the major cause of prosthetic join implant loosening. Recent advances in our understanding of cellular and molecular mechanisms of periprosthetic osteolysis have highlighted cytokine release and osteoclast function controlled by numerous intracellular signaling pathway, one of which is nuclear factor kappa B (NFjB). Direct inhibition of NFjB is an efficient therapy to block bone erosion associated with inflammatory arthritis. There are no approved nonoperative treatments for periprosthetic osteolysis. Gene therapy, however, offers novel possibilities. As the implant interface cells are located in the closed joint space, intra-articular injection of siRNA (small interfering RNA) is accessible as local administration to avoid systemic side effect. We postulate that local administration of siRNA for NFjB could inhibit wear particles-induced inflammatory osteolysis. In our opinion, this gene therapy seems to hold interesting future prospects for effective therapeutic interventions in humans. c 2008 Elsevier Ltd. All rights reserved. Background sary. However, revision surgery is associated with significant cost and potential morbidity risk [1– Hip arthroplasty is an effective surgery to treat pa- 3]. Wear part