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积雪草苷是积雪草的一种成分,可通过 NFATc1 和 NF-κB 信号通路来抑制 RANKL 诱导的破骨细胞生成。

Asiaticoside, a component of Centella asiatica attenuates RANKL-induced osteoclastogenesis via NFATc1 and NF-κB signaling pathways.

机构信息

Department of Orthopaedics, Affiliated Foshan Hospital, Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong, China.

The Third Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong, China.

出版信息

J Cell Physiol. 2019 Apr;234(4):4267-4276. doi: 10.1002/jcp.27195. Epub 2018 Aug 26.

Abstract

Identification of natural compounds that inhibit osteoclastogenesis will facilitate the development of antiresorptive treatment of osteolytic bone diseases. Asiaticoside is a triterpenoid derivative isolated from Centella asiatica, which exhibits varying biological effects like angiogenesis, anti-inflammation, wound healing, and osteogenic differentiation. However, its role in osteoclastogenesis remains unknown. Here, we show that Asiaticoside can suppress RANKL-induced osteoclast formation and bone resorption in a dose-dependent manner. Asiaticoside attenuated the expression of osteoclast marker genes including Ctsk, Atp6v0d2, Nfatc1, Acp5, and Dc-stamp. Furthermore, Asiaticoside inhibited RANKL-mediated NF-κB and NFATc1 activities, and RANKL-induced calcium oscillation. Collectively, this study demonstrates that Asiaticoside inhibited osteoclast formation and function through attenuating RANKL-induced key signaling pathways, which may indicate that Asiaticoside is a potential antiresorptive agent against osteoclast-related osteolytic bone diseases.

摘要

鉴定能抑制破骨细胞生成的天然化合物将有助于开发治疗溶骨性骨疾病的抗吸收药物。积雪草酸是一种从积雪草中分离出来的三萜衍生物,具有多种生物学效应,如血管生成、抗炎、伤口愈合和成骨分化。然而,其在破骨细胞生成中的作用尚不清楚。在这里,我们表明积雪草酸可以剂量依赖性地抑制 RANKL 诱导的破骨细胞形成和骨吸收。积雪草酸减弱了破骨细胞标志物基因的表达,包括 Ctsk、Atp6v0d2、Nfatc1、Acp5 和 Dc-stamp。此外,积雪草酸抑制了 RANKL 介导的 NF-κB 和 NFATc1 活性以及 RANKL 诱导的钙振荡。总之,这项研究表明,积雪草酸通过减弱 RANKL 诱导的关键信号通路来抑制破骨细胞的形成和功能,这可能表明积雪草酸是一种针对与破骨细胞相关的溶骨性骨疾病的潜在抗吸收剂。

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