NF‐κB decoy oligodeoxynucleotide inhibits wear particle‐induced inflammation in a murine calvarial model

Abstract Wear particles induce periprosthetic inflammation and osteolysis through activation of nuclear factor kappa B (NF‐κB), which up‐regulates the downstream target gene expression for proinflammatory cytokines in macrophages. It was hypothesized that direct suppression of NF‐κB activity in the early phases of this disorder could be a therapeutic strategy for preventing the inflammatory response to wear particles, potentially mitigating osteolysis. NF‐κB activity can be suppressed via competitive binding with double stranded NF‐κB decoy oligodeoxynucleotides (ODNs) that blocks this transcription factor from binding to the promoter regions of targeted genes. In this murine calvarial study, clinically relevant polyethylene particles (PEs) with/without ODN were subcutaneously injected over the calvarial bone. In the presence of PE particles, macrophages migrated to the inflammatory site and induced tumor necrosis factor alpha (TNF‐α) and receptor activator of nuclear factor kappa B ligand (RANKL) expression, resulting in an increase in the number of osteoclasts. Local injections of ODN mitigated the expression of TNF‐α, RANKL, and induced the expression of two anti‐inflammatory, antiresorptive cytokines: interleukin‐1 receptor antagonist and osteoprotegerin. Local intervention with NF‐κB decoy ODN in early cases of particle‐induced inflammation in which the prosthesis is still salvageable may potentially preserve periprosthetic bone stock. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3872–3878, 2015.