维生素K对成骨细胞骨形成和破骨细胞骨吸收的影响
投稿时间:2020-01-17  修订日期:2020-04-13  点此下载全文
引用本文:蒋益忠,夏天爽,辛海量,金玉娥,蒋益萍,薛黎明.维生素K对成骨细胞骨形成和破骨细胞骨吸收的影响[J].药学实践杂志,2020,38(4):340~345
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作者单位E-mail
蒋益忠 浙江省东阳市中医院, 浙江 东阳 322105  
夏天爽 海军军医大学药学院生药学教研室, 上海 200433  
辛海量 海军军医大学药学院生药学教研室, 上海 200433  
金玉娥 上海市疾病预防控制中心化学品毒性检定所, 上海 200336  
蒋益萍 海军军医大学药学院生药学教研室, 上海 200433 msjyp@163.com 
薛黎明 上海市疾病预防控制中心化学品毒性检定所, 上海 200336 lm.xue@hotmail.com 
基金项目:上海市卫生和计划生育委员会面上项目(201740068)
中文摘要:目的 比较维生素K1(VK1)、维生素K2(MK4)、维生素K2(MK7)和维生素K3(VK3)促进骨形成和抑制骨吸收的作用。方法 采用新生大鼠颅盖骨分离成骨细胞和以核因子κB受体活化因子配体(RANKL)诱导骨髓单核细胞的破骨细胞为模型,用磷酸苯二钠法检测成骨碱性磷酸酶(ALP)和抗酒石酸酸性磷酸酶(TRAP)活性;用CellTilter试剂盒检测破骨细胞代谢活力;用Z-FR-MCA荧光底物和胶原底物降解检测组织蛋白酶K(CTSK)抑制作用。结果 MK4和MK7在0.1~1 μmol/L时显著促进成骨细胞增殖(P<0.05),1 μmol/L时显著提高ALP活性和骨结节形成面积,VK3抑制了骨结节形成(P<0.05)。VK1、VK3、MK4和MK7在1 μmol/L时对破骨细胞代谢活力均无影响,MK4和MK7在0.1~1 μmol/L时显著抑制TRAP活性(P<0.05),而VK1和VK3无抑制作用。MK4在25 μmol/L可对CTSK与Z-FR-MCA底物结合的抑制率达58.9%,在100 μmol/L对CTSK胶原降解的抑制率达73.2%。结论 相较于VK1和VK3,MK7和MK4有显著促进成骨细胞活性和抑制破骨细胞骨吸收的作用,MK4能显著抑制破骨细胞CTSK酶活性。
中文关键词:维生素K  骨质疏松  成骨细胞  破骨细胞
 
Effects of vitamin K on osteoblastic bone formation and osteoclastic bone absorption
Abstract:Objective To compare the effects of vitamin K1 (VK1), vitamin K2 (MK4), vitamin K2 (MK7) and vitamin K3 (VK3) on bone formation and bone absorption.Methods Osteoblasts were isolated from calvaria of newborn rats and osteoclasts were induced by receptor activator of nuclear factor-κ B ligand (RANKL). ALP and TRAP activity were measured by diphenyl phosphate method. Osteoclast metabolic activity was measured by Celltiter kit. The inhibition of cathepsin K (CTSK) was measured by Z-FR-MCA fluorescent substrate and collagen substrate degradation.Results MK4 and MK7 at 0.1~1 μmol/L significantly increased the proliferation of osteoblasts (P<0.05) and at 1 μmol/L increased ALP activity and bone nodule formation area. VK3 inhibited bone nodule formation (P<0.05). VK1,VK3,MK4 and MK7 at 1 μmol/L had no effect on osteoclastic bone absorption. MK4 and MK7 significantly inhibited TRAP activity at 0.1~1 μmol/L (P<0.05), while VK1 and VK3 did not show the inhibitory effect. The inhibition of MK4 at 25 μmol/L on CTSK binding to Z-FR-MCA substrate activity is 58.9% and the inhibition of MK4 at 100 μmol/L on collagen degradation of CTSK activity is 73.2%.Conclusion Compared with VK1 and VK3, MK7 and MK4 significantly increase osteoblast activity and inhibit osteoclast bone absorption, MK4 inhibits osteoclast CTSK enzyme activity.
keywords:vitamin K  osteoporosis  osteoblasts  osteoclasts
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