Bavachalcone inhibits osteoclast differentiation through suppression of NFATc1 induction by RANKL
Bavachalcone inhibits osteoclast differentiation through suppression of NFATc1 induction by RANKL
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巴伐醌通过抑制 RANKL 诱导 NFATc1 来抑制破骨细胞分化
DOI：
10.1016/j.bcp.2008.03.007
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发表时间：
2008-06-01
影响因子：
5.8
通讯作者：
Kim, Hong-Hee
中科院分区：
文献类型：
--
作者：
Park, Cheol Kyu;Lee, Youngkyun;Kim, Hong-Hee
破骨细胞是对骨吸收具有专门作用的细胞，并且是许多骨疾病如骨质疏松症的原因。由于草药产品是发现用于新疗法的化合物的宝贵来源，我们试图从涉及治疗骨质疏松症的药用植物中鉴定有效抑制破骨细胞生成的化合物。巴伐查尔酮是从补骨脂中分离得到的一种有效成分，采用破骨细胞前体细胞的原代培养方法研究其对破骨细胞分化的影响。此外，还研究了其作用的分子机制。巴伐查尔酮抑制破骨细胞形成的前体细胞的IC 50类似于1.5 μ g ml（-1）。在巴瓦查尔酮存在下，核因子κ B配体（RANKL）受体激活剂（破骨细胞分化因子）对MEK、ERK和Akt的激活显著降低。破骨细胞生成的关键转录因子c-Fos和NFATc 1通过RANKL的诱导也被巴瓦查尔酮抑制。总之，巴瓦查尔酮通过干扰ERK和Akt信号通路以及在分化过程中诱导c-Fos和NFATc 1来抑制破骨细胞生成。我们的结果表明巴瓦查酮可用作骨吸收相关疾病的治疗药物。(C)2008年爱思唯尔公司All rights reserved.
Osteoclasts are cells that have a specialized role for bone resorption and are responsible for many bone diseases such as osteoporosis. As herbal products are invaluable sources in discovery of compounds for new therapies, we sought to identify compounds efficacious in suppressing osteoclastogenesis from medicinal plants that have been implicated for treatment of osteoporotic conditions. Bavachalcone was isolated from Psoralea corylifolia, and its effects on osteoclast differentiation were evaluated with primary cultures of osteoclast precursor cells. In addition, the molecular mechanism of action was investigated. Bavachalcone inhibited osteoclast formation from precursor cells with the IC50 of similar to 1.5 mu g ml(-1). The activation of MEK, ERK, and Akt by receptor activator of nuclear factor kappaB ligand (RANKL), the osteoclast differentiation factor, was prominently reduced in the presence of bavachalcone. The induction of c-Fos and NFATc1, key transcription factors for osteoclastogenesis, by RANKL was also suppressed by bavachalcone. In conclusion, bavachalcone inhibits osteoclastogenesis by interfering with the ERK and Akt signaling pathways and the induction of c-Fos and NFATc1 during differentiation. our results suggest that bavachalcone may be useful as a therapeutic drug for bone resorption-associated diseases. (C) 2008 Elsevier Inc. All rights reserved.