Epidermal growth factor receptor promotes osteoclast differentiation probably through regulating ABCC1 and CDC37
10.16016/j.2097-0927.202312125
- VernacularTitle:表皮生长因子受体可能通过调控ABCC1和CDC37的表达促进破骨细胞分化
- Author:
Xin TAN
1
;
Ziyuan ZHANG
;
Xing LIU
Author Information
1. 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
- Keywords:
epidermal growth factor receptor;
osteoclast differentiation;
ATP binding cassette subfamily C member 1;
cell division cycle 37
- From:
Journal of Army Medical University
2024;46(19):2171-2179
- CountryChina
- Language:Chinese
-
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 differentiation of mouse osteoclasts(P＜0.01).RNA-seq data indicated that EGFR expression was significantly associated with multiple signaling pathways,including MAPK pathway(P＜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)(P＜0.01).The osteoclast differentiation model showed significant increases in the expression levels of ABCC1(P＜0.05)and CDC37(P＜0.01)during differentiation,and activation of EGFR further enhanced the levels(P＜0.01)while EGFR inhibition decreased them(P＜0.05).Conclusion Activation of EGFR signal induces osteoclast differentiation and up-regulates the expression levels of ABCC1 and CDC37.
