[1]章文娟,谢保平,李伟娟,等.补骨脂素抑制破骨细胞形成及其机制的实验研究[J].陆军军医大学学报(原第三军医大学学报),2017,39(07):641-645.
　Zhang Wenjuan,Xie Baoping,Li Weijuan,et al.Inhibitory effect of psoralen on osteoclast formation and its underlying mechanism in vitro[J].J Amry Med Univ (J Third Mil Med Univ),2017,39(07):641-645.
点击复制

补骨脂素抑制破骨细胞形成及其机制的实验研究(/HTML )
分享到：

陆军军医大学学报（原第三军医大学学报）[ISSN:1000-5404/CN:51-1095/R]

卷:
39卷
期数:
2017年第07期
页码:
641-645
栏目:
基础医学
出版日期:
2017-04-15

文章信息/Info

Title:
Inhibitory effect of psoralen on osteoclast formation and its underlying mechanism in vitro
作者:
章文娟; 谢保平; 李伟娟; 李劲平; 甘国兴; 张杰
中南大学：湘雅药学院，湘雅三医院药剂科；清远市中医院药剂科
Author(s):
Zhang Wenjuan;  Xie Baoping;  Li Weijuan;  Li Jingping;  Gan Guoxing;  Zhang Jie

Xiangya School of Pharmaceutical Science, Department of Pharmacy, Third Xiangya Hospital, Central South University, Changsha, Hunan Province, 410013; Department of Pharmacy, Qingyuan Hospital of Traditional Chinese Medicine, Qingyuan, Guangdong Province, 511500, China

关键词:
补骨脂素; 破骨细胞; RAW264.7; 雌激素受体; IL-17
Keywords:
psoralen;  osteoclasts;  RAW264.7 cells;  estrogen receptor-α  IL-17R 
分类号:
R285.5; R329.6; R681
文献标志码:
A
摘要:

目的     探讨补骨脂素对破骨细胞分化的影响，以及对破骨细胞ERα、IL-17R基因表达的调节作用，初步阐明补骨脂素抗骨质疏松作用。方法     采用核因子κB受体活化因子配体体外诱导小鼠巨噬细胞RAW264.7分化为破骨细胞，以雌二醇作为阳性对照药，补骨脂素分为高剂量（10 μmol/L）、中剂量（5 μmol/L）、低剂量（2.5 μmol/L）。通过TRAP染色细胞数和骨吸收陷窝数评价药物抑制破骨细胞分化作用，同时采用RT-PCR和ELISA检测破骨细胞MMP-9、Cathepsin K、TRAP基因表达和蛋白水平，反映破骨细胞活性，RT-PCR和ELISA检测IL-17R、ER-α的基因表达和蛋白水平，初步探讨补骨脂素作用机制。结果     与对照组比较，补骨脂素高、中、低3个浓度均显著抑制破骨细胞形成数和骨陷窝形成数，同时对Cathepsin K、TRAP、IL-17R的基因表达均有显著的抑制作用(P<0.05， P<0.01），并且显著增强ER-α基因表达（P<0.01）。高、中、低剂量的补骨脂素对MMP9的基因表达有显著的抑制作用(P<0.05）。与对照组比较，高、中剂量的补骨脂素对Cathepsin K的蛋白含量有非常显著的抑制作用（P<0.01）；高、中、低剂量的补骨脂素对TRAP、MMP-9、IL-17R的蛋白含量有显著的抑制作用(P<005， P<0.01）；高、中、低剂量的补骨脂素均显著促进ER-α的蛋白表达（P<0.01）。结论     补骨脂素对破骨细胞的形成和溶骨活性均有显著的抑制作用，该作用可能通过提高破骨细胞雌激素受体的表达和抑制IL17R的表达实现。

Abstract:

Objective     To determine the effect of psoralen on osteoclast differentiation and on the regulation of ER-alpha and IL-17R in the osteoclasts in order to preliminary clarify the anti-osteoporosis effect of psoralen. Methods     In order to induce the differentiation of to osteoclasts, mouse macrophage RAW264.7 cells were divided into 5 groups, and treated respectively with receptor activator for nuclear factor-κB ligand (RANKL), RANKL+estradiol (positive control), and RANKL+psoralen at 3 different concentrations (10, 5 and 2.5 μmol/L). In 5 d after the treatment, tartrate-resistant acid phosphatase (TRAP) staining and bone resorption essay were used to identify the inhibitory effects of psoralen on the differentiation of osteoclasts. Transcriptional and protein concentration levels of matrix metallopeptidase 9 (MMP-9), TRAP and Cathepsin K were detected by RT-PCR and ELISA to clarify the activity of osteoclasts, and the expression of IL-17R and estrogen receptor-α (ER-α) was also detected for the role of psoralen in the process. Results      Compared with control cells, high-, middle- and low-dose psoralen significantly inhibited the numbers of osteoclasts and osteoclastmediated bone resorption, as well as the gene expression of Cathepsin K, TRAP and IL-17R (P<0.05, P<0.01), while markedly enhanced the expression of ER-α (P<0.01). The 3 doses of psoralen also reduced the MMP-9 expression significantly (P<0.05). Compared with the control group, the protein level of Cathepsin K was very significantly decreased in the high- and middle-dose psoralen groups (P<0.01). The treatment of psoralen at 3 doses also markedly reduced the protein contents of TRAP, MMP-9 and IL-17R (P<0.05, P<0.01), and promoted that of ER-α (P<0.01). Conclusion      Psoralen remarkably inhibits the differentiation of osteoclasts and the function of osteolysis at the same time, which might be due to its enhancing the expression of ER and suppressing that of IL-17R.

相似文献/References:

[1]陈莉丽,黄玫,雷利红,等.OPG/RANKL/RANK系统参与牙槽骨吸收及重建过程作用初探[J].陆军军医大学学报(原第三军医大学学报),2013,35(04):288.
　Chen Lili,Huang Mei,Lei Lihong,et al.Role of OPG/RANKL/RANK system during alveolar bone resorption and remodeling[J].J Amry Med Univ (J Third Mil Med Univ),2013,35(07):288.
[2]王晓军,王爱民.OPG/RANKL/RANK系统与人工关节无菌性松动[J].陆军军医大学学报(原第三军医大学学报),2006,28(04):373.
[3]廖通权,刘玉刚,胡旭,等.CD147对体外破骨细胞分化成熟的影响[J].陆军军医大学学报(原第三军医大学学报),2010,32(24):2623.
　Liao Tongquan,Liu Yugang,Hu Xu,et al.Effect of CD147 on differentiation and maturation of osteoclasts in vitro[J].J Amry Med Univ (J Third Mil Med Univ),2010,32(07):2623.
[4]钱奕铭,初同伟,周跃,等.强直性脊柱炎滑膜细胞破骨表型及分化因素的研究[J].陆军军医大学学报(原第三军医大学学报),2008,30(23):2207.
　QIAN Yi-ming,CHU Tong-wei,ZHOU Yue,et al.Osteoclast phenotypes and differentiation factors of synoviocyte in ankylosing spondylitis[J].J Amry Med Univ (J Third Mil Med Univ),2008,30(07):2207.
[5]黄晓斌,仲蕾蕾.破骨细胞钠氢转运蛋白关键位点研究[J].陆军军医大学学报(原第三军医大学学报),2012,34(13):1273.
　Huang Xiaobin,Zhong Leilei.Key point of Na+-H+ antiporter to transport sodium in osteoclast[J].J Amry Med Univ (J Third Mil Med Univ),2012,34(07):1273.
[6]刘栓得,初同伟,张超,等.血小板衍生生长因子D对体外破骨细胞分化过程的影响[J].陆军军医大学学报(原第三军医大学学报),2013,35(11):1067.
　Liu Shuande,Chu Tongwei,Zhang Chao,et al.Platelet-derived growth factor-D induces differentiation and maturation in osteoclastsin vitro[J].J Amry Med Univ (J Third Mil Med Univ),2013,35(07):1067.
[7]雷利红,黄玫,吴燕岷,等.EphrinB2/EphB4在牙槽骨吸收-重建过程中的作用[J].陆军军医大学学报(原第三军医大学学报),2013,35(21):2331.
　Lei Lihong,Huang Mei,Wu Yanmin,et al.Role of EphrinB2/EphB4 during alveolar bone resorption and remodeling[J].J Amry Med Univ (J Third Mil Med Univ),2013,35(07):2331.
[8]代飞,吴军.免疫系统与骨代谢的关系[J].陆军军医大学学报(原第三军医大学学报),2005,27(02):175.
[9]余世明,初同伟,廖通权,等.CD147对体外破骨细胞分化过程中基质金属蛋白酶-2、基质金属蛋白酶-9分泌的影响[J].陆军军医大学学报(原第三军医大学学报),2011,33(14):1492.
　Yu Shiming,Chu Tongwei,Liao Tongquan,et al.Effect of exogenous CD147 protein on synthesis and secretion of matrix metalloproteinases-2 and 9 during differentiation and maturation of osteoclasts in vitro[J].J Amry Med Univ (J Third Mil Med Univ),2011,33(07):1492.
[10]李晓刚,苏楠,唐玉彬,等.FGF2对破骨细胞体外分化以及骨吸收功能的直接调控作用[J].陆军军医大学学报(原第三军医大学学报),2014,36(07):636.
　Li Xiaogang,Su Nan,Tang Yubin,et al.Fibroblast growth factor 2 directly regulates osteoclast differentiation and bone resorption function[J].J Amry Med Univ (J Third Mil Med Univ),2014,36(07):636.

更新日期/Last Update: 2017-04-07