The number of total joint replacements is increasing, especially in elderly patients, and so too are implant-related complications such as prosthesis loosening. 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-ĸB decoy oligodeoxynucleotides (ODN), mesenchymal stem cells (MSCs), and genetically-modified NF-ĸB sensing interleukin-4 over-secreting MSCs (IL4-MSCs) 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 (15−17 months old) for 6 weeks. Local delivery of ODN showed increased bone mineral density (BMD), decreased osteoclast-like cells, increased alkaline phosphatase (ALP)-positive area, and increased M2/M1 macrophage ratio. Local injection of MSCs and IL4-MSCs significantly decreased osteoclast-like cells and increased the M2/M1 ratio, with a greater trend for IL4-MSCs than MSCs. MSCs significantly increased ALP-positive area and BMD values compared with the control. The IL4-MSCs demonstrated higher values for both ALP-positive area and BMD. These findings demonstrated the therapeutic effects of ODN, MSCs, and IL4-MSCs on chronic inflammatory osteolysis in aged mice. The two MSC-based 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-MSCs were more effective in mitigating inflammation. This study suggests potential therapeutic strategies for treating wear particle-associated inflammatory osteolysis after arthroplasty in the elderly.

中文翻译：

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间充质干细胞、转基因间充质干细胞和 NFĸB 抑制剂对老年小鼠慢性炎症性骨溶解的治疗作用


全关节置换术的数量正在增加，尤其是老年患者，假体松动等与植入相关的并发症也在增加。假体的磨损颗粒会引起慢性炎症反应和随后的骨质溶解，导致需要进行修复手术。本研究调查了 NF-ĸB 诱饵寡脱氧核苷酸 (ODN)、间充质干细胞 (MSC) 和转基因 NF-ĸB 感应白细胞介素 4 过度分泌 MSC (IL4-MSC) 对老年小鼠慢性炎症的治疗作用。该模型是通过将受污染的聚乙烯颗粒连续注入老年小鼠（15-17 个月大）股骨远端髓内空间 6 周而生成的。 ODN 的局部递送显示骨矿物质密度 (BMD) 增加、破骨细胞样细胞减少、碱性磷酸酶 (ALP) 阳性面积增加以及 M2/M1 巨噬细胞比率增加。局部注射MSCs和IL4-MSCs显着减少破骨细胞样细胞并增加M2/M1比率，其中IL4-MSCs的趋势比MSCs更大。与对照组相比，MSC 显着增加了 ALP 阳性面积和 BMD 值。 IL4-MSC 表现出较高的 ALP 阳性面积和 BMD 值。这些发现证明了 ODN、MSC 和 IL4-MSC 对老年小鼠慢性炎症性骨溶解的治疗作用。这两种基于 MSC 的疗法在增加 M2/M1 巨噬细胞比率、减少骨吸收和增加骨形成方面比 ODN 更有效。具体来说，MSC 在增加骨形成方面更有效，而 IL4-MSC 在减轻炎症方面更有效。 这项研究提出了治疗老年人关节置换术后磨损颗粒相关的炎症性骨溶解的潜在治疗策略。