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Vaccarin 通过阻断 NF-κB 和 MAPK 信号通路来预防钛颗粒诱导的骨溶解并抑制 RANKL 诱导的破骨细胞生成。

Vaccarin prevents titanium particle-induced osteolysis and inhibits RANKL-induced osteoclastogenesis by blocking NF-κB and MAPK signaling pathways.

机构信息

Department of Orthopaedics, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.

Research Centre for Regenerative Medicine, Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi, China.

出版信息

J Cell Physiol. 2019 Aug;234(8):13832-13842. doi: 10.1002/jcp.28063. Epub 2019 Jan 13.

DOI:10.1002/jcp.28063
PMID:30637734
Abstract

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-κB 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.

摘要

钛颗粒诱导破骨细胞形成,伴随种植体周围骨溶解,是髋关节假体长期失效的主要原因。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、副作用更小的新药是极其紧迫的。舞茸素是从金顶侧耳中提取的一种天然黄酮类化合物,具有多种生物学功能,包括抗氧化、抗炎和促进血管生成。然而,舞茸素在抑制钛颗粒诱导的骨溶解中的作用尚未报道。在这项研究中,表明舞茸素可以在体外有效抑制 RANKL 诱导的破骨细胞分化、F-肌动蛋白环融合、骨吸收以及破骨细胞标记基因的表达,呈剂量依赖性。此外,舞茸素还可以通过抑制 NF-κB 和 MAPK(p38、ERK 和 JNK)信号通路来抑制 RANKL 诱导的破骨细胞分化,并抑制下游转录因子如 c-Fos 和 NFATc1 的转录。与体外结果一致,这项体内研究表明,舞茸素通过抗破骨细胞形成对钛颗粒诱导的骨溶解具有抑制作用。总之,舞茸素可能是预防和治疗种植体周围骨溶解的一种有前途的药物。

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