Bergapten suppresses RANKL-induced osteoclastogenesis and ovariectomy-induced osteoporosis via suppression of NF-κB and JNK signaling pathways
Bergapten suppresses RANKL-induced osteoclastogenesis and ovariectomy-induced osteoporosis via suppression of NF-κB and JNK signaling pathways
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Bergapten 通过抑制 NF-kappa B 和 JNK 信号通路来抑制 RANKL 诱导的破骨细胞生成和卵巢切除术诱导的骨质疏松症
DOI：
10.1016/j.bbrc.2018.12.112
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发表时间：
2019-02-05
影响因子：
3.1
通讯作者：
Liu, Xuqiang
中科院分区：
文献类型：
--
作者：
Chen, Guiping;Xu, Qiang;Liu, Xuqiang
佛手内酯（Bergapten，BP）是蛇床子（Cnidium monnieri（L）Cusson）的一种有效成分，具有重要的生物活性和药理作用。然而，BP对卵巢切除引起的骨质疏松症的影响及其机制尚不完全清楚。本研究通过体内外实验研究了BP对卵巢切除所致骨质疏松的影响及对核因子-κ B配体受体激活剂（RANKL）诱导破骨细胞生成的影响，并探讨其作用机制。我们发现BP治疗对卵巢切除引起的骨质疏松症在体内产生有益的影响。此外，BP减弱了骨髓巨噬细胞（BTH）和RAW 264.7细胞中的破骨细胞生成，而没有任何细胞毒性。此外，BP特异性抑制RANKL诱导的NF-κ B和JNK信号传导，但不抑制p38和ERK。在mRNA水平上，BP抑制OC相关转录因子NFATcl和c-fos，从而影响OC分化相关基因的表达。此外，BP破坏了F-肌动蛋白环的形成，这对骨吸收活性很重要，并损害OC骨吸收。因此，BP可能是绝经后骨质疏松症的一种有用的替代疗法。(C)2018爱思唯尔公司All rights reserved.
Bergapten (BP), derived from Cnidium monnieri (L) Cusson, is an ingredient widely used in traditional Chinese medicine and has important biological and pharmacological activities. However, the effect of BP on ovariectomy-induced osteoporosis and the underlying mechanism are not entirely clear. In this study, we investigated the effects of BP on ovariectomy-induced osteoporosis and receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis in vivo and in vitro, and explored the underlying mechanism. We found that BP treatment exerted beneficial effects on ovariectomy-induced osteoporosis in vivo. Further, BP attenuated osteoclastogenesis in bone marrow macrophages (BMMs) and RAW264.7 cells without any cytotoxicity. Additionally, BP specifically inhibited RANKL-induced NF-KB and JNK signaling,but did not suppress p38 and ERK. At the mRNA level, BP inhibits the OC-associated transcription factor NFATcl and c-fos, thereby affecting the expression of OC differentiation-related genes. Moreover, BP disrupted the formation of F-actin rings, which are important for bone-resorbing activity, and impairs OC bone resorption. Therefore, BP may be a useful alternative therapy for postmenopausal osteoporosis. (C) 2018 Elsevier Inc. All rights reserved.