Vaccarin prevents titanium particle-induced osteolysis and inhibits RANKL-induced osteoclastogenesis by blocking NF-B and MAPK signaling pathways
Vaccarin prevents titanium particle-induced osteolysis and inhibits RANKL-induced osteoclastogenesis by blocking NF-B and MAPK signaling pathways
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Vaccarin 通过阻断 NF-B 和 MAPK 信号通路来防止钛颗粒诱导的骨溶解并抑制 RANKL 诱导的破骨细胞生成
DOI：
10.1002/jcp.28063
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发表时间：
2019-08-01
影响因子：
5.6
通讯作者：
Liu, Qian
中科院分区：
文献类型：
--
作者：
Liu, Yun;Song, Fang-Ming;Liu, Qian
人工髋关节假体长期失效的主要原因是佩戴钛颗粒诱导的破骨细胞生成，并伴有种植体周围骨溶解。目前，用于预防和治疗种植体周围骨溶解的药物显示出严重的副作用。因此，开发更有效、副作用更少的新药迫在眉睫。金合欢素是一种从三叶越桔中提取的天然黄酮类化合物，具有抗氧化、抗炎、促进血管生成等多种生物学功能。然而，维卡林在抑制钛颗粒诱导的骨溶解中的作用尚未见报道。本研究表明，维拉帕林在体外能有效抑制RANKL诱导的破骨细胞生成、F-肌动蛋白环融合、骨吸收和破骨细胞标志物基因的表达，且呈剂量依赖关系。此外，维拉帕林还可通过抑制NF-B和MAPK(p38、ERK和JNK)信号通路抑制RANKL诱导的破骨细胞生成，并抑制下游转录因子c-Fos和NFATc1的转录。与体外实验结果一致的是，体内研究表明，维卡林通过抗破骨细胞生成抑制钛颗粒诱导的骨溶解。综上所述，维菌素可作为预防和治疗种植体周围骨溶解的一种有前景的药物。
Wearing titanium particle-induced osteoclastogenesis, accompanied by peri-implant osteolysis, is the main cause of long-term failure of hip prosthesis. Currently, medications used for the prevention and treatment of peri-implant osteolysis show serious side effects. Therefore, development for more effective new drugs with less side effects is extremely urgent. Vaccarin is a natural flavonoid extracted from Vaccaria segetalis, with various biological functions, including antioxidantory, anti-inflammatory, and promotion of angiogenesis. However, the putative role of vaccarin in the inhibition of titanium particle-induced osteolysis has not been reported. In this study, it was indicated that vaccarin could effectively inhibit RANKL-induced osteoclastogenesis, fusion of F-actin rings, bone resorption, and expression of osteoclast marker genes in a dose-dependent manner in vitro. Moreover, vaccarin could also inhibit RANKL-induced osteoclastogenesis via the inhibition of NF-B and MAPK (p38, ERK, and JNK) signaling pathways, and inhibit the transcription of downstream transcription factors, such as c-Fos and NFATc1. Consistent with in vitro results, this in vivo study showed that vaccarin exhibited an inhibitory effect on titanium particle-induced osteolysis by antiosteoclastogenesis. In conclusion, vaccarin could be a promising agent for preventing and treating peri-implant osteolysis.