Kaempferide Prevents Titanium Particle Induced Osteolysis by Suppressing JNK Activation during Osteoclast Formation.

Kaempferide Prevents Titanium Particle Induced Osteolysis by Suppressing JNK Activation during Osteoclast Formation.
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DOI:
10.1038/s41598-017-16853-w
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发表时间:
2017-11-30
期刊:
影响因子:
4.6
通讯作者:
Yang C
Yang C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Jiao Z;Xu W;Zheng J;Shen P;Qin A;Zhang S;Yang C

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山奈素(KF)是一种O-甲基化的黄酮醇,是一种天然植物提取物,通常存在于山奈中。它具有多种作用,包括抗癌,抗炎,抗氧化,抗菌和抗病毒特性。在这项研究中,我们的目的是调查是否KF有效地抑制钛颗粒诱导的颅骨骨丢失通过下调JNK信号通路。在钛颗粒诱导的小鼠颅骨溶解模型中,KF低剂量组的骨吸收小凹轻度减少,而高剂量组的骨吸收小凹较少。组织学检查显示KF组破骨细胞形成较少。KF在12.5 μM浓度下显著抑制小鼠骨髓巨噬细胞(BMSCs)和RAW264.7细胞中破骨细胞的形成和骨吸收。然而,KF不影响成熟的破骨细胞F-肌动蛋白环的形成。但当与KF和茴香霉素共同处理时,BMMs分化为成熟的破骨细胞。在分子水平上,JNK磷酸化受到抑制,破骨细胞生成相关的特异性基因V-ATP酶d2、TRAP、降钙素受体(CTR)、c-Fos和NFATc 1的表达受到明显抑制。总之,这些结果表明,KF是一种有前途的药物在治疗破骨细胞相关疾病。
Kaempferide (KF) is an O-methylated flavonol, a natural plant extract, which is often found in Kaempferia galanga. It has a variety of effects including anti-carcinogenic, anti-inflammatory, anti-oxidant, anti-bacterial and anti-viral properties. In this study, we aimed to investigate whether KF effectively inhibits titanium particle induced calvarial bone loss via down regulation of the JNK signaling pathway. In the mice with titanium particle induced calvarial osteolysis, the Low dose of KF mildly reduced the resorption pits while in the high dose group, fewer scattered pits were observed on the surface of calvarium. Histological examination showed fewer osteoclasts formation in the KF group. In mouse bone marrow macrophages (BMMs) and RAW264.7 cells, KF significantly inhibited the osteoclast formation and bone resorption at 12.5 μM. However, KF does not affect the mature osteoclast F-actin ring formation. But when being co-treated with KF and anisomycin, BMMs differentiated into mature osteoclasts. At the molecular levels, the JNK phosphorylation was inhibited and the osteoclastogenesis-related specific gene expression including V-ATPase d2, TRAP, calcitonin receptor (CTR), c-Fos and NFATc1 was markedly suppressed. In conclusion, these results indicated that KF is a promising agent in the treatment of osteoclast-related diseases.
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