Curcumin Inhibits Polyethylene-Induced Osteolysis via Repressing NF-κB Signaling Pathway Activation
Curcumin Inhibits Polyethylene-Induced Osteolysis via Repressing NF-κB Signaling Pathway Activation
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DOI：
10.1159/000494537
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发表时间：
2018-01-01
影响因子：
--
通讯作者：
Wang, Long
中科院分区：
文献类型：
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作者：
An, Senbo;Han, Fei;Wang, Long
背景/目的：无菌性松动是全髋关节置换术后人工髋关节置换失败的常见原因。无菌性松动主要是磨损碎片造成的，磨损碎片会导致骨溶解并削弱支撑假体的结构。磨损碎片在松动过程中的骨溶解中起着至关重要的作用，聚乙烯 (PE) 颗粒比任何其他类型的颗粒更频繁地作为磨损碎片被发现。在缺乏有效治疗药物的情况下，骨溶解一直难以治疗。先前的研究表明，姜黄素在破骨细胞生成过程中影响信号体相关激酶和蛋白酶体泛素系统。本研究的目的是探讨姜黄素的抗骨质溶解作用，并在可能的情况下确定 PE 诱导骨质溶解模型中涉及的信号通路。方法：体外用 PE 颗粒在 RAW264.7（单核细胞/巨噬细胞）细胞中诱导破骨细胞分化，并在体内通过 PE 刺激建立的颅骨和气囊骨溶解模型诱导破骨细胞分化。我们进行了一组 TRAP 染色、实时聚合酶链反应 (PCR) 和蛋白质印迹实验，通过比较暴露和未暴露于姜黄素的标本来评估姜黄素的抗骨质溶解作用。结果：姜黄素对磨损碎片引起的骨质溶解具有良好的抑制作用，并抑制 RANK/c-Fos/NFATc1 信号通路。结论：姜黄素可以预防PE引起的骨溶解和骨丢失。对 RANK/c-Fos/NFATc1 信号通路的抑制作用可以解释姜黄素的抗骨质溶解活性。 (C) 2018 作者由巴塞尔 S. Karger AG 出版。
Background/Aims: Aseptic loosening is a common reason for failed artificial hip replacement after total hip arthroplasty. Aseptic loosening is mostly the result of wear debris that causes osteolysis and weakens the structures that support the prosthesis. Wear debris plays a crucial role in osteolysis during the loosening process, and polyethylene (PE) particles are found as wear debris more frequently than any other type of particle. In the absence of effective therapeutic agents, osteolysis has been hard to treat. Previous studies have demonstrated that curcumin influences signalosome-associated kinases and the proteasome-ubiquitin system during osteoclastogenesis. The aims of this study were to explore the anti-osteolysis effect of curcumin and if possible to identify the signaling pathway involved in a model of PEinduced osteolysis. Methods: Differentiation of osteoclasts was induced in vitro by PE particles in RAW264.7 (monocyte/macrophage) cells and in vivo by calvarial and air pouch models of osteolysis established by PE stimulation in mice. We performed a set of TRAP staining, realtime polymerase chain reaction (PCR), and Western blot experiments to evaluate the antiosteolytic effect of curcumin by comparing specimens that were exposed and not exposed to curcumin. Results: Curcumin had a promising inhibitory effect on osteolysis induced by wear debris and suppressed the RANK/c-Fos/NFATc1 signaling pathway. Conclusion: Curcumin can prevent PE-induced osteolysis and bone loss. An inhibitory effect on the RANK/c-Fos/NFATc1 signaling pathway may explain the anti-osteolysis activity of curcumin. (C) 2018 The Author(s) Published by S. Karger AG, Basel.