title: 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.
authors.affiliation: Department of Orthopaedic Surgery, Stanford University, Stanford, California.
authors.forename: Taishi
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Orthopaedic Surgery, Stanford University, Stanford, California.
authors.forename: Jukka
authors.initials: J
authors.lastname: Pajarinen
authors.affiliation: Department of Orthopaedic Surgery, Stanford University, Stanford, California.
authors.forename: Tzu-hua
authors.initials: TH
authors.lastname: Lin
authors.affiliation: Department of Orthopaedic Surgery, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Tamaki
authors.affiliation: Department of Orthopaedic Surgery, Stanford University, Stanford, California.
authors.forename: Florence
authors.initials: F
authors.lastname: Loi
authors.affiliation: Department of Cardiovascular Research, Development, and Translational Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Egashira
authors.affiliation: Department of Orthopaedic Surgery, Stanford University, Stanford, California.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Department of Orthopaedic Surgery, Stanford University, Stanford, California.|Department of Bioengineering, Stanford University, Stanford, California.
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Goodman
mesh_terms: D000818:Animals; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use*; D009924:Organ Culture Techniques; D010316:Particle Size; D020959:Polyethylene / Q000032:analysis / Q000276:immunology*; D012886:Skull / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology
chemical_list: D016328:NF-kappa B; C468119:NF-kappaB decoy; D009838:Oligodeoxyribonucleotides; D020959:Polyethylene
keywords: NF-κB; murine calvarial model; osteolysis; total joint replacement; wear particles