Abstract

Wear particles induce periprosthetic inflammation and osteolysis through activation of Nuclear Factor kappa B (NF-?B) in macrophages, which up-regulates the downstream target gene expression for pro-inflammatory cytokines. It is hypothesized that direct suppression of NF-?B activity in the early phases of this disorder is a therapeutic strategy for mitigating the inflammatory response to wear particles, potentially mitigating osteolysis. NF-?B activity can be suppressed via competitive binding with double stranded NF-?B decoy oligodeoxynucleotides (ODNs) that block 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-a) 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-a, RANKL, and induced the expression of two anti-inflammatory, anti-resorptive cytokines: Interleukin-1 receptor antagonist (IL-1ra) and Osteoprotegerin (OPG). Local intervention with NF-?B decoy ODN in early cases of particle-induced inflammation in which the prosthesis is still salvageable may potentially preserve periprosthetic bone stock. This article is protected by copyright. All rights reserved.

View details for DOI 10.1002/jbm.a.35532

View details for Web of Science ID 000363879200018

View details for PubMedID 26123702