[1α,25-二羟维生素D3对人成骨细胞中基质金属蛋白酶及组织金属蛋白酶抑制剂的调控作用]

[The effects of 1alpha,25-dihydroxyvitamin D3 in regulation matrix metalloproteinase and tissue metalloproteinase inhibitors in human osteoblasts].

作者信息

Guo Li-juan, Luo Xiang-hang, Xie Hui, Zhou Hou-de, Liao Er-yuan

机构信息

Institute of Endocrinology & Metabolism, the Second Xiangya Hospital of Central South Medical University, Changsha 410011, China.

出版信息

Zhonghua Nei Ke Za Zhi. 2005 Feb;44(2):125-8.

PMID:15840226

Abstract

OBJECTIVE

To characterize the effects of 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] on the expression of matrix metalloproteinase (MMP)-1, MMP-2, membrane-type MMP-1 (MT1-MMP), tissue inhibitors of metalloproteinase-1 (TIMP-1) in human osteoblast, and understand the mechanism by which 1alpha,25(OH)2D3 exert on bone.

METHODS

Osteoblasts were interfered by 1alpha,25(OH2D3. Western blot were used to show the action of 1alpha,25(OH)2D3 on the expression of MT1-MMP protein in human osteoblasts. ELISA was done to examine the effect of 1alpha,25(OH)2D3 on the activity of MMP-2. Northern blot analysis was performed to detect vitamin D receptor mRNA levels and to evaluate the effect of 1alpha,25(OH)2D3 on MT1-MMP mRNA levels.

RESULTS

The results showed that 1alpha,25(OH)2D3 had no effect on the expression of MMP-1, MMP-2 and TIMP-1 in human osteoblasts; 10(-10) - 10(-8) mol/L 1alpha,25(OH)2D3 induced MT1-MMP expression in a dose-dependent manner (P < 0.05), 10(-10) - 10(-8) mol/L 1alpha,25(OH)2D3 induced the activation of proMMP-2 in a dose-dependent manner in human osteoblasts[The activity of MMP-2 was (42.3 +/- 8.6), (64.4 +/- 11.4), (93.5 +/- 9.9) microg/L respectively, P < 0.05].

CONCLUSION

1alpha,25(OH)2D3 may stimulate bone resorption by inducing MT1-MMP production in osteoblasts.

摘要

目的

研究1α,25 - 二羟维生素D3[1α,25(OH)2D3]对人成骨细胞中基质金属蛋白酶（MMP）-1、MMP-2、膜型MMP-1（MT1-MMP）及金属蛋白酶组织抑制剂-1（TIMP-1）表达的影响，以了解1α,25(OH)2D3作用于骨骼的机制。

方法

用1α,25(OH)2D3干预成骨细胞。采用蛋白质免疫印迹法检测1α,25(OH)2D3对人成骨细胞中MT1-MMP蛋白表达的作用。采用酶联免疫吸附测定法检测1α,25(OH)2D3对MMP-2活性的影响。进行Northern印迹分析检测维生素D受体mRNA水平，并评估1α,25(OH)2D3对MT1-MMP mRNA水平的影响。

结果

结果显示，1α,25(OH)2D3对人成骨细胞中MMP-1、MMP-2及TIMP-1的表达无影响；10^(-10) - 10^(-8) mol/L的1α,25(OH)2D3以剂量依赖方式诱导MT1-MMP表达（P < 0.05），10^(-10) - 10^(-8) mol/L的1α,25(OH)2D3以剂量依赖方式诱导人成骨细胞中前MMP-2的激活[MMP-2活性分别为(42.3 ± 8.6)、(64.4 ± 11.4)、(93.5 ± 9.9) μg/L，P < 0.05]。