Curcumin Attenuation of Wear Particle-Induced Osteolysis via RANKL Signaling Pathway Suppression in Mouse Calvarial Model.
Curcumin Attenuation of Wear Particle-Induced Osteolysis via RANKL Signaling Pathway Suppression in Mouse Calvarial Model.
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DOI：
10.1155/2017/5784374
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发表时间：
2017
影响因子：
4.6
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Cheng T;Zhao Y;Li B;Cheng M;Wang J;Zhang X
磨粒诱导的慢性炎症和破骨细胞形成是骨溶解过程中的两个关键因素。姜黄素(Cur)是药用植物姜黄的活性化合物，具有抗炎和抗破骨作用。本研究采用小鼠颅骨溶解模型，在体内和体外验证了Cur可减轻聚甲基丙烯酸甲酯(PMMA)诱导的炎性骨溶解的假说。将小鼠分为4组：磷酸盐缓冲盐水组、CUR组、PMMA组和PMMA + CUR组。在植入聚甲基丙烯酸甲酯微粒前3d，小鼠腹腔注射Cur(25 mg/kg/d)。术后10天，取小鼠颅骨进行显微计算机断层扫描、组织形态计量学和分子生物学分析。正如预期的那样，Cur显著减少了颅骨器官培养中肿瘤坏死因子-α、白介素1β和白介素6的分泌。此外，与PMMA刺激的颅骨相比，Cur抑制了体内破骨细胞的形成，减少了骨吸收。此外，Cur还下调PMMA颗粒刺激小鼠破骨细胞特异性基因的表达，逆转核因子-kappa-B受体激活剂(RANKL)/护骨素信使RNA和蛋白质的比例。这些结果提示，Cur通过抑制RANKL信号通路减轻PMMA颗粒诱导的小鼠颅骨炎性骨溶解，可能是防治AL的候选化合物。
Wear particle-induced chronic inflammation and osteoclastogenesis are two critical factors in the osteolytic process. Curcumin (CUR) is an active compound of the medicinal herb Curcuma longa and has anti-inflammatory and antiosteoclastogenic properties. Our study tested the hypothesis that CUR might attenuate polymethylmethacrylate- (PMMA-) induced inflammatory osteolysis using mouse calvaria osteolysis model in vivo and in vitro. The mice were divided into four groups: phosphate-buffered saline group, CUR, PMMA, and PMMA + CUR groups. Three days before PMMA particle implantation, the mice were intraperitoneally injected with CUR (25 mg/kg/day). Ten days after the operation, the mouse calvaria was harvested for microcomputed tomography, histomorphometry, and molecular biology analysis. As expected, CUR markedly reduced the secretion of tumor necrosis factor-α, interleukin- (IL-) 1β, and IL-6 in the calvarial organ culture. Moreover, CUR suppressed osteoclastogenesis and decreased bone resorption in vivo compared with PMMA-stimulated calvaria. Furthermore, CUR downregulated the osteoclast-specific gene expression and reversed the receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin messenger RNA and protein ratio in PMMA particle-stimulated mice. These results suggest that CUR attenuated PMMA particle-induced inflammatory osteolysis by suppressing the RANKL signaling pathway in the murine calvarium, which could be a candidate compound to prevent and treat AL.
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