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

Taishi Sato, Jukka Pajarinen, Tzu Hua Lin, Yasunobu Tamaki, Florence Loi, Kensuke Egashira, Zhenyu Yao, Stuart B. Goodman

    Research output: Contribution to journalArticlepeer-review

    19 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)3872-3878
    Number of pages7
    JournalJournal of Biomedical Materials Research - Part A
    Volume103
    Issue number12
    DOIs
    Publication statusPublished - Dec 2015

    All Science Journal Classification (ASJC) codes

    • Ceramics and Composites
    • Biomaterials
    • Biomedical Engineering
    • Metals and Alloys

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