{"doi":"10.1002/jbm.a.37175","title":"Suppression of <scp>NF‐κB</scp>‐induced chronic inflammation mitigates inflammatory osteolysis in the murine continuous polyethylene particle infusion model","abstract":"Wear particle-associated bone loss (periprosthetic osteolysis) constrains the longevity of total joint arthroplasty (TJA). Wear particles induce a prolonged upregulation of nuclear factor kappa B (NF-κB) signaling in macrophages and osteoclasts. Synthetic double-stranded oligodeoxynucleotides (ODNs) can prevent the binding of NF-κB to the promoter regions of targeted genes and inhibit genetic activation. We tested the hypothesis that polyethylene-particle induced chronic inflammatory bone loss could be suppressed by local delivery of NF-κB decoy ODNs in murine in vivo model. Polyethylene particles were continuously infused into the medullary cavity of the distal femur for 6 weeks to induce chronic inflammation, and micro-computational tomography and immunohistochemical analysis were performed. Particle-induced chronic inflammation resulted in lower BMD values, an increase in osteoclastogenesis and nuclear translocation of p65, a prolonged M1 pro-inflammatory macrophage phenotype, and a decrease of M2 anti-inflammatory macrophage phenotype. Delayed timing of local infusion of NF-κB decoy ODN for the last 3 weeks reversed polyethylene-particle associated chronic inflammatory bone loss and facilitated bone healing. This study demonstrated that polyethylene-particle associated chronic inflammatory osteolysis can be effectively modulated via interference with the NF-κB pathway; this minimally invasive intervention could potentially be an efficacious therapeutic strategy for periprosthetic osteolysis after TJA.","journal":"Journal of Biomedical Materials Research Part A","year":2021,"id":176260,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9463,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":456618,"name":"Ning Zhang","orcid":"0000-0002-9513-9288","position":1,"is_corresponding":false},{"id":457928,"name":"Tzuhua Lin","orcid":null,"position":2,"is_corresponding":false},{"id":456616,"name":"Yusuke Kohno","orcid":"0000-0003-1821-4560","position":3,"is_corresponding":false},{"id":456615,"name":"Masaya Ueno","orcid":"0000-0002-4121-9127","position":4,"is_corresponding":false},{"id":355415,"name":"Masahiro Maruyama","orcid":"0000-0002-1339-0023","position":5,"is_corresponding":false},{"id":457929,"name":"Ejun Huang","orcid":null,"position":6,"is_corresponding":false},{"id":357205,"name":"Claire Rhee","orcid":null,"position":7,"is_corresponding":false},{"id":355418,"name":"Zhenyu Yao","orcid":"0000-0002-1144-0621","position":8,"is_corresponding":false},{"id":231542,"name":"Stuart B. Goodman","orcid":"0000-0002-1919-3717","position":9,"is_corresponding":false},{"id":456617,"name":"Takeshi Utsunomiya","orcid":"0000-0002-9770-9803","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-18T23:47:19.591542Z","pmid":"33779115","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}