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Wear particles from the prosthesis induce a chronic inflammatory reaction and subsequent osteolysis, leading to the need for revision surgery. This study investigated the therapeutic effect of NF\u2010\u0138B decoy oligodeoxynucleotides (ODN), mesenchymal stem cells (MSCs), and genetically\u2010modified NF\u2010\u0138B sensing interleukin\u20104 over\u2010secreting MSCs (IL4\u2010MSCs) on chronic inflammation in aged mice. The model was generated by continuous infusion of contaminated polyethylene particles into the intramedullary space of the distal femur of aged mice (15\u221217 months old) for 6 weeks. Local delivery of ODN showed increased bone mineral density (BMD), decreased osteoclast\u2010like cells, increased alkaline phosphatase (ALP)\u2010positive area, and increased M2\/M1 macrophage ratio. Local injection of MSCs and IL4\u2010MSCs significantly decreased osteoclast\u2010like cells and increased the M2\/M1 ratio, with a greater trend for IL4\u2010MSCs than MSCs. MSCs significantly increased ALP\u2010positive area and BMD values compared with the control. The IL4\u2010MSCs demonstrated higher values for both ALP\u2010positive area and BMD. These findings demonstrated the therapeutic effects of ODN, MSCs, and IL4\u2010MSCs on chronic inflammatory osteolysis in aged mice. The two MSC\u2010based therapies were more effective than ODN in increasing the M2\/M1 macrophage ratio, reducing bone resorption, and increasing bone formation. Specifically, MSCs were more effective in increasing bone formation, and IL4\u2010MSCs were more effective in mitigating inflammation. This study suggests potential therapeutic strategies for treating wear particle\u2010associated inflammatory osteolysis after arthroplasty in the elderly.<\/jats:p>","DOI":"10.1002\/jor.25434","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T02:48:40Z","timestamp":1661741320000},"page":"1004-1013","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Therapeutic effects of MSCs, genetically modified MSCs, and NF\u0138B\u2010inhibitor on chronic inflammatory osteolysis in aged mice"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0738-1569","authenticated-orcid":false,"given":"Junichi","family":"Kushioka","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery Stanford University School of Medicine  Stanford California 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