NFkappaB gene silencing inhibits wear particles-induced inflammatory osteolysis.

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 (NFkappaB). Direct inhibition of NFkappaB 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 NFkappaB 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.