Protection Effect of Curcumin for Macrophage-Involved Polyethylene Wear Particle-Induced Inflammatory Osteolysis by increasing the Cholesterol Efflux
Protection Effect of Curcumin for Macrophage-Involved Polyethylene Wear Particle-Induced Inflammatory Osteolysis by increasing the Cholesterol Efflux
复制标题
姜黄素通过增加胆固醇流出对巨噬细胞相关的聚乙烯磨损颗粒诱导的炎症性骨溶解的保护作用
DOI：
10.12659/msm.914197
复制
发表时间：
2019-01-01
影响因子：
3.1
通讯作者：
Hu, Yi-he
中科院分区：
文献类型：
--
作者：
Liu, Yu-wei;An, Sen-bo;Hu, Yi-he
背景：由磨损颗粒和炎症引起的假体周围骨溶解是原发性关节置换术失败的常见原因。姜黄素是一种来自植物的天然酚，据报道可以减少巨噬细胞的炎症。本研究旨在探讨姜黄素对巨噬细胞参与、磨损颗粒诱导的骨溶解的潜在影响及其机制。材料/方法：采用RAW264.7巨噬细胞，检测聚乙烯（PE）颗粒和姜黄素对巨噬细胞胆固醇外排及表型改变的影响。建立PE颗粒诱导小鼠颅骨骨溶解模型，观察姜黄素在体内的作用。治疗14 d后，采用显微ct （micro- computer tomography, micro-CT）和组织学分析患处骨质量，并从细胞和分子水平分析骨周围软组织。结果：我们发现PE颗粒可以刺激巨噬细胞的破骨细胞形成，并在体外产生m1样表型。姜黄素增强巨噬细胞内胆固醇外排，在PE颗粒作用下维持m0样表型。此外，姜黄素在体内可增强胆固醇跨膜调节因子ABCA1、ABCG1和CAV1。我们还发现，在我们的小鼠骨溶解模型中，姜黄素治疗组骨密度增强，破骨细胞生成减少，炎症反应减少。结论：姜黄素可以通过促进胆固醇外排来抑制巨噬细胞参与的骨溶解和炎症。维持胆固醇外排可能是预防全关节置换术后假体周围骨溶解的潜在策略。
Background: Periprosthetic osteolysis, induced by wear particles and inflammation, is a common reason for failure of primary arthroplasty. Curcumin, a nature phenol from plants, has been reported to reduce the inflammation in macrophages. This study aimed to investigate the potential effect of curcumin on macrophage involved, wear particle-induced osteolysis and its mechanism.Material/Methods: RAW264.7 macrophages were used to test the effects of polyethylene (PE) particles and curcumin on macrophage cholesterol efflux and phenotypic changes. A mouse model of PE particle-induced calvarial osteolysis was established to test the effects of curcumin in vivo. After 14 days of treatment, the bone quality of the affected areas was analyzed by micro-computed tomography (micro-CT) and histology, and the bone surrounding soft tissues were analyzed at the cellular and molecular levels.Results: We found that PE particles can stimulate osteoclastogenesis and produce an M1-like phenotype in macrophages in vitro. Curcumin enhanced the cholesterol efflux in macrophages, and maintained the M0-like phenotype under the influence of PE particles in vitro. Additionally, the cholesterol transmembrane regulators ABCA1, ABCG1, and CAV1 were enhanced by curcumin in vivo. We also found enhanced bone density, reduced osteoclastogenesis, and fewer inflammatory responses in the curcumin treated groups in our mouse osteolysis model.Conclusions: Our study findings indicated that curcumin can inhibit macrophage involved osteolysis and inflammation via promoting cholesterol efflux. Maintaining the cholesterol efflux might be a potential strategy to prevent periprosthetic osteolysis after total joint arthroplasty surgery.