Cepharanthine suppresses osteoclast formation by modulating the nuclear factor-B and nuclear factor of activated T-cell signaling pathways
Cepharanthine suppresses osteoclast formation by modulating the nuclear factor-B and nuclear factor of activated T-cell signaling pathways
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Cepharanthine 通过调节核因子-kappaB 和激活的 T 细胞信号通路的核因子来抑制破骨细胞形成。
DOI：
10.1002/jcb.27495
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发表时间：
2019-02-01
影响因子：
4
通讯作者：
Liu, Qian
中科院分区：
文献类型：
--
作者：
Lin, Xixi;Song, Fangming;Liu, Qian
破骨细胞活化增强是几种溶骨性疾病的主要表现，包括骨质疏松、类风湿性关节炎、骨科植入物无菌性松动、Paget病和恶性骨病。这些疾病的一种重要的骨保护疗法是抑制破骨细胞分化和吸收功能。鉴于现有药物的有害副作用，从天然化合物中寻找有效和安全的药物是有益的。千金藤碱(CEP)是从千金藤中提取的一种化合物，已被发现具有抗氧化和抗炎作用。在本研究中，我们通过破骨细胞生成和骨吸收实验发现，CEP抑制核因子-B受体激活剂配体(RANKL)诱导的破骨细胞形成和骨吸收活性。通过聚合酶链式反应，我们还发现CEP抑制了破骨细胞分化标志基因CTSK、Calcr、Atp6v0d2、Mmp9和Nfarc1的表达。免疫印迹和荧光素酶报告实验等机制分析表明，CEP抑制RANKL诱导的核因子-B和活化T细胞的核因子活化，而核因子是破骨细胞形成所必需的。总体而言，这些数据表明CEP有可能被用作预防或治疗溶骨性疾病的替代疗法。
The increased activation of osteoclasts is the major manifestation of several lytic bone diseases, including osteoporosis, rheumatoid arthritis, aseptic loosening of orthopedic implants, Paget disease and malignant bone diseases. One important bone-protective therapy in these diseases focuses on the inhibition of osteoclast differentiation and resorptive function. Given that the deleterious side-effects of currently available drugs, it is beneficial to search for effective and safe medications from natural compounds. Cepharanthine (CEP) is a compound extracted from Stephania japonica and has been found to have antioxidant and anti-inflammatory effects. In this study, we found that CEP inhibited receptor activator of nuclear factor-B (NF-B) ligand (RANKL)-induced osteoclast formation and bone-resorbing activities using osteoclastogenesis and bone resorption assay. By polymerase chain reaction, we also found that CEP inhibited the expression of osteoclast-differentiation marker genes including Ctsk, Calcr, Atp6v0d2, Mmp9 and Nfatc1. Mechanistic analyses including Western blot and luciferase reporter assay revealed that CEP inhibited RANKL-induced activation of NF-B and nuclear factor of activated T-cell, which are essential for the formation of osteoclast. Collectively, these data suggested that CEP can potentially be used as an alternative therapy for preventing or treating osteolytic diseases.