1, 25(OH)<sub>2</sub>D<sub>3</sub>通过抑制IκB/NF-κB信号通路抑制破骨细胞生成

邓杰忠; 杨宇生; 何晋月; 罗飞; 许建中; 张泽华

doi:10.16016/j.1000-5404.202102035

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1, 25(OH)₂D₃通过抑制IκB/NF-κB信号通路抑制破骨细胞生成

基础医学 | 更新时间：2026-02-13

- 1, 25(OH)₂D₃通过抑制IκB/NF-κB信号通路抑制破骨细胞生成
- 1, 25(OH)₂D₃ inhibits osteoclastogenesis by IκB/NF-κB signaling pathway
- 第三军医大学学报 2021年43卷第14期页码：1339-1345
- 作者机构：
  
  400038 重庆，陆军军医大学(第三军医大学)第一附属医院骨科
- 作者简介：
  
  [ 张泽华，E-mail: zhangzehuatmmu@163.com ZHANG Zehua, E-mail: zhangzehuatmmu@163.com
- 基金信息：
  
  国家自然科学基金面上项目(81772365)
- DOI：10.16016/j.1000-5404.202102035
  中图分类号： Q565;R322.71;R329.25
- 收稿：2021-02-05，
  
  修回：2021-04-09，
  
  纸质出版：2021-07-30
- 稿件说明：
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邓杰忠, 杨宇生, 何晋月, 等. 1, 25(OH)₂D₃通过抑制IκB/NF-κB信号通路抑制破骨细胞生成[J]. 第三军医大学学报, 2021,43(14):1339-1345.

Jiezhong DENG, Yusheng YANG, Jinyue HE, et al. 1, 25(OH)₂D₃ inhibits osteoclastogenesis by IκB/NF-κB signaling pathway[J]. Journal of Third Military Medical University, 2021, 43(14): 1339-1345.
邓杰忠, 杨宇生, 何晋月, 等. 1, 25(OH)₂D₃通过抑制IκB/NF-κB信号通路抑制破骨细胞生成[J]. 第三军医大学学报, 2021,43(14):1339-1345. DOI： 10.16016/j.1000-5404.202102035.

Jiezhong DENG, Yusheng YANG, Jinyue HE, et al. 1, 25(OH)₂D₃ inhibits osteoclastogenesis by IκB/NF-κB signaling pathway[J]. Journal of Third Military Medical University, 2021, 43(14): 1339-1345. DOI： 10.16016/j.1000-5404.202102035.

摘要

目的

研究维生素D和维生素D受体(vitamin D receptor，VDR)在破骨细胞分化各阶段的作用及其机制。

方法

从C57BL/6小鼠四肢骨骨髓中提取原代单核巨噬细胞(bone marrow derived macrophages，BMMs)，使用核因子κ B受体活化因子配体(receptor activator of nuclear kappa B ligand，RANKL)和巨噬细胞集落刺激因子(macrophage colony-stlimulating factor，M-CSF)将BMMs诱导成破骨细胞。同时使用不同浓度(0.1、10、1 000 nmol/L)的1

25(OH)

进行干预，激活VDR。采用TRAP和FAK染色、噬骨实验、qPCR和Western blot等实验分析1

25(OH)

对破骨细胞生成的影响。

结果

25(OH)

作为VDR的强激动剂，在1 000 nmol/L时能高效激活VDR，在mRNA和蛋白水平均抑制破骨细胞分化早期c-Fos和NFATc1的表达，以及抑制成熟期CtsK和MMP-9的表达(

0.05)。1 000 nmol/L 1

25(OH)

显著下调IκB α的磷酸化水平(

0.05)，从而抑制p65的核转位与磷酸化。

结论

1 000 nmol/L 1

25(OH)

显著上调VDR的表达，1

25(OH)

激活VDR可通过IκB α/ NF-κB p65信号通路抑制破骨细胞分化、融合和骨吸收活性。

Abstract

Objective

To investigate the role and mechanism of vitamin D and vitamin D receptor (VDR) in various stages of osteoclastogenesis.

Methods

First

bone marrow derived macrophages (BMMs) were extracted from the bone marrow of the femurs and tibias of C57BL/6 mice

and the BMMs were induced into osteoclasts by receptor activator of nuclear kappa B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). At the same time

different concentrations of 1

25(OH)

(0.1

10 and 1 000 nmol/L) were added to activate VDR. TRAP and FAK staining

pit formation assay

qPCR and Western blotting were performed in this study.

Results

25(OH)

as a strong agonist of VDR

effectively activated VDR at a dose of 1 000 nmol/L and inhibited the expression of c-Fos and NFATc1 at mRNA and protein levels at the early stage of osteoclast differentiation

and also inhibited the expression of CtsK and MMP9 at mature stage (

0.05). The dose significantly down-regulated the phosphorylation of IκBα (

0.05)

and thereby suppressed the nuclear translocation and phosphorylation of p65.

Conclusion

25(OH)

at 1 000 nmol/L significantly up-regulates the expression of VDR

and activates VDR to inhibit osteoclast differentiation

fusion and bone resorption activity through the IκBα/NF-κB p65 signaling pathway.

关键词

Keywords

references

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DOI：10.16016/j.1000-5404.202102035

摘要

Abstract

关键词

Keywords

references

1, 25(OH)₂D₃通过抑制IκB/NF-κB信号通路抑制破骨细胞生成

1, 25(OH)₂D₃ inhibits osteoclastogenesis by IκB/NF-κB signaling pathway