Epidermal growth factor receptor promotes osteoclast differentiation probably through regulating ABCC1 and CDC37

Xin TAN; Ziyuan ZHANG; Xing LIU

doi:10.16016/j.2097-0927.202312125

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Epidermal growth factor receptor promotes osteoclast differentiation probably through regulating ABCC1 and CDC37

Basic Medicine | 更新时间：2026-01-09

- Epidermal growth factor receptor promotes osteoclast differentiation probably through regulating ABCC1 and CDC37
- Journal of Army Medical University Vol. 46, Issue 19, Pages: 2171-2179(2024)
- 作者机构：
  
  400014 重庆，重庆医科大学附属儿童医院骨科，儿童发育疾病研究教育部重点实验室，重庆市干细胞治疗工程技术研究中心
- 作者简介：
- 基金信息：
- DOI：10.16016/j.2097-0927.202312125
  CLC： R322.71;R329.28;R394.2
- Received：22 December 2023，
  
  Revised：2024-06-21，
  
  Published：15 October 2024
- 稿件说明：
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Xin TAN, Ziyuan ZHANG, Xing LIU. Epidermal growth factor receptor promotes osteoclast differentiation probably through regulating ABCC1 and CDC37[J]. Journal of Army Medical University, 2024, 46(19): 2171-2179.
DOI：

Xin TAN, Ziyuan ZHANG, Xing LIU. Epidermal growth factor receptor promotes osteoclast differentiation probably through regulating ABCC1 and CDC37[J]. Journal of Army Medical University, 2024, 46(19): 2171-2179. DOI： 10.16016/j.2097-0927.202312125.

摘要

目的

观察表皮生长因子受体(epidermal growth factor receptor

EGFR)在小鼠破骨细胞分化过程中的表达趋势，探究破骨细胞分化过程中EGFR相关信号通路及关键基因。

方法

从24只6~8周龄健康SPF级雄性C57BL/6小鼠(体质量19~21g)中提取骨髓来源巨噬细胞，随后采用M-CSF和RANKL共刺激构建小鼠破骨细胞分化模型，并用TRAP染色法、RT-qPCR检测破骨细胞分化状况及EGFR的表达量变化。通过生物信息学方法系统鉴定破骨细胞分化过程中EGFR相关基因，并通过RT-qPCR和EGFR激活及抑制模型进行验证。

结果

体外破骨细胞分化模型显示，EGFR在小鼠破骨细胞分化过程中表达量持续上升(

＜0.01)。RNA-seq数据表明，EGFR表达与MAPK等多条信号通路呈显著相关(

＜0.05)。通过WGCNA及PPI分析，鉴定出ATP结合盒亚家族C成员1 (ATP binding cassette subfamily C member 1

ABCC1)和细胞分裂周期蛋白37(cell division cycle 37

CDC37)与EGFR之间存在共表达及相关性(

＜0.01)。RT-qPCR检测结果显示，ABCC1(

＜0.05)和CDC37(

＜0.01)在分化过程中表达量显著上升，且在激活EGFR时二者表达水平进一步升高(

＜0.01)，抑制EGFR时二者表达明显降低(

＜0.05)。

结论

激活EGFR信号可诱导破骨细胞分化，并上调ABCC1和CDC37的表达水平。

Abstract

Objective

To observe the expression profile of epidermal growth factor receptor (EGFR) during the differentiation of osteoclasts

and to explore EGFR-related signaling pathways and key genes during the process.

Methods

Bone marrow derived macrophages were extracted from 24 healthy SPF-grade male C57BL/6 mice (6-8 weeks old

weighing 19~21 g)

and then treated with M-CSF and RANKL co-stimulation to establish a model of mouse osteoclast differentiation. TRAP staining and RT-qPCR were used to detect the differentiation status of osteoclasts and the expression level of EGFR. Bioinformatics were employed to systematically identify EGFR-related genes during osteoclast differentiation

and then RT-qPCR and EGFR activation and inhibition models were applied to validate the genes.

Results

In vitro

osteoclast differentiation model showed the EGFR expression level was in a continuous increase during the differenti

ation of mouse osteoclasts (

0.01). RNA-seq data indicated that EGFR expression was significantly associated with multiple signaling pathways

including MAPK pathway (

0.05). Weighted correlation network analysis (WGCNA) and protein-protein interaction (PPI) analysis identified co-expression and correlations of EGFR with ATP binding cassette subfamily C member 1 (ABCC1) and cell division cycle 37 (CDC37) (

0.01). The osteoclast differentiation model showed significant increases in the expression levels of ABCC1 (

0.05) and CDC37 (

0.01) during differentiation

and activation of EGFR further enhanced the levels (

0.01) while EGFR inhibition decreased them (

0.05).

Conclusion

Activation of EGFR signal induces osteoclast differentiation and up-regulates the expression levels of ABCC1 and CDC37.

关键词

Keywords

references

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