Interferon Regulatory Factor 4 (IRF4) Plays a Key Role in Osteoblast Differentiation of Postmenopausal Osteoporosis

Xuan Wu; Cuicui Yang; Xiangxu Chen; Zhengming Shan; Xiaotao Wu

doi:10.31083/j.fbl2903115

Frontiers in Bioscience-Landmark (Mar 2024)

Interferon Regulatory Factor 4 (IRF4) Plays a Key Role in Osteoblast Differentiation of Postmenopausal Osteoporosis

Xuan Wu,
Cuicui Yang,
Xiangxu Chen,
Zhengming Shan,
Xiaotao Wu

Affiliations

Xuan Wu: Department of Orthopedics, Zhong Da Hospital, School of Medicine, Southeast University, 210009 Nanjing, Jiangsu, China
Cuicui Yang: Research Center for Bone and Stem Cells; Key Laboratory for Aging & Disease; Nanjing Medical University, 211166 Nanjing, Jiangsu, China
Xiangxu Chen: Department of Orthopedics, Zhong Da Hospital, School of Medicine, Southeast University, 210009 Nanjing, Jiangsu, China
Zhengming Shan: Department of Orthopedics, Zhong Da Hospital, School of Medicine, Southeast University, 210009 Nanjing, Jiangsu, China
Xiaotao Wu: Department of Orthopedics, Zhong Da Hospital, School of Medicine, Southeast University, 210009 Nanjing, Jiangsu, China

DOI: https://doi.org/10.31083/j.fbl2903115
Journal volume & issue: Vol. 29, no. 3
p. 115

Abstract

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Background: Postmenopausal osteoporosis (PMOP) is a prevalent disease, which features decreased bone mass, bone weakness and deteriorated bone microstructure in postmenopausal women. Although many factors have been revealed to contribute to the occurrence of PMOP, its mechanism remains undefined. This work aimed to identify significant changes in gene expression during PMOP formation and to examine the most valuable differential genes in postmenopausal osteoporosis versus the control group. Methods: The GSE68303 dataset that contains 12 ovariectomize (OVX) experimental and 11 sham groups was downloaded and analyzed. The results indicated that interferon regulatory factor 4 (IRF4) might be a hub gene in the development of postmenopausal osteoporosis. Western blot and immunohistochemistry were carried out to evaluate IRF4 levels in thoracic vertebra extracts from OVX and Sham mice. To assess IRF4’s impact on osteogenic differentiation in postmenopausal bone marrow mesenchymal stem cells (BM-MSCs), IRF4 overexpression (OV-IRF4) and knockdown (Sh-IRF4) plasmids were constructed. Results: The results showed that comparing with the sham group, bone samples from the OVX group showed higher IRF4 expression. Alkaline phosphatase (ALP) staining revealed that IRF4 overexpression significantly inhibited ALP activity, while IRF4 knockdown promoted ALP activity in BM-MSCs. Simvastatin-treated OVX mice showed increased total bone volume/total tissue volume (BV/TV) and elevated Runx2 expression by immunohistochemical staining compared with the OVX group. Conclusions: This study demonstrated that IRF4 is associated with OVX induced osteoporosis, it can regulate bone stability by inhibiting the osteogenic differentiation BM-MSCs. This study may help enhance our understanding of the molecular mechanism of PMOP formation, providing new insights into estrogen defiance induced osteoporosis.

Published in Frontiers in Bioscience-Landmark

ISSN: 2768-6701 (Print); 2768-6698 (Online)
Publisher: IMR Press
Country of publisher: Singapore
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry; Science: Biology (General)
Website: https://www.imrpress.com/journal/FBL

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