Local delivery of mutant CCL2 protein-reduced orthopaedic implant wear particle-induced osteolysis and inflammation in vivo.
Local delivery of mutant CCL2 protein-reduced orthopaedic implant wear particle-induced osteolysis and inflammation in vivo.
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DOI：
10.1002/jor.22977
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发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Yang F
中科院分区：
文献类型：
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作者：
Jiang X;Sato T;Yao Z;Keeney M;Pajarinen J;Lin TH;Loi F;Egashira K;Goodman S;Yang F
全关节置换术（TJR）已被广泛用作晚期关节炎的标准治疗方法。 TJR 长期疗效面临的一项挑战是种植体表面会产生超高分子量聚乙烯磨损颗粒，从而激活炎症级联反应，可能导致骨质流失、假体松动并最终导致手术失败。在这里，我们使用小鼠颅骨模型研究局部施用突变型 CCL2 蛋白（例如 7ND）对减少磨损颗粒引起的体内炎症和骨溶解的功效。每隔一天对小鼠局部注射 7ND 或磷酸盐缓冲盐水 (PBS)，持续长达 14 天。使用显微 CT、组织学和免疫荧光染色评估磨损颗粒诱导的骨溶解和 7ND 治疗的效果。与 PBS 对照相比，7ND 处理显着减少了磨损颗粒引起的骨溶解，从而导致更高的骨体积分数和骨矿物质密度。此外，免疫荧光染色显示 7ND 治疗减少了募集的炎症细胞和破骨细胞的数量。总之，我们的结果支持局部递送 7ND 来减轻磨损颗粒引起的炎症和骨溶解的可行性，这可能为延长 TJR 的使用寿命提供有前途的策略。
Total joint replacement (TJR) has been widely used as a standard treatment for late-stage arthritis. One challenge for long-term efficacy of TJR is the generation of ultra-high molecular weight polyethylene wear particles from the implant surface that activates an inflammatory cascade which may lead to bone loss, prosthetic loosening and eventual failure of the procedure. Here, we investigate the efficacy of local administration of mutant CCL2 proteins, such as 7ND, on reducing wear particle-induced inflammation and osteolysis in vivo using a mouse calvarial model. Mice were treated with local injection of 7ND or phosphate buffered saline (PBS) every other day for up to 14 days. Wear particle-induced osteolysis and the effects of 7ND treatment were evaluated using micro-CT, histology, and immunofluorescence staining. Compared with the PBS control, 7ND treatment significantly decreased wear particle-induced osteolysis, which led to a higher bone volume fraction and bone mineral density. Furthermore, immunofluorescence staining showed 7ND treatment decreased the number of recruited inflammatory cells and osteoclasts. Together, our results support the feasibility of local delivery of 7ND for mitigating wear particle-induced inflammation and osteolysis, which may offer a promising strategy for extending the life time of TJRs.