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Overexpression of RUNX1 mitigates dexamethasone-induced impairment of osteogenic differentiation and oxidative stress injury in bone marrow mesenchymal stem cells by promoting alpha-2 macroglobulin transcription

QINGJIAN HE1, HUIXIN ZHU2,3, SHANHONG FANG4,5,*

1 Department of Bone Joint and Sports Medicine, Fuzhou Hospital of Traditional Chinese Medicine Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, 350001, China
2 Nursing Department, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350004, China
3 Nursing Department, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital of Fujian Medical University, Fuzhou, 350004, China
4 Department of Orthopedic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350004, China
5 Department of Sports Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital of Fujian Medical University, Fuzhou, 350004, China

* Corresponding Author: SHANHONG FANG. Email: email

BIOCELL 2024, 48(2), 205-216. https://doi.org/10.32604/biocell.2023.045109

Abstract

Introduction: Dexamethasone (Dex) caused impaired osteoblast differentiation and oxidative stress (OS) in bone marrow mesenchymal stem cells (BMSCs). This work sought to elucidate the precise molecular pathway through which Dex influences osteogenic differentiation (OD) and OS in BMSCs. Methods: The expression of Runt-related transcription factor 1 (RUNX1) and alpha-2 macroglobulin (A2M) was assessed in Dex-treated BMSCs using qRT-PCR and Western Blot. Following the functional rescue experiments, cell proliferation was determined by MTT assay, reactive oxygen species (ROS) expression by DCFH-DA fluorescent probe, lactate dehydrogenase (LDH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (Gpx) expression by kits, OD by alkaline phosphatase (ALP) staining and activity quantification, and the expression of OD-related proteins RUNX2, collagen type 1 alpha 1 (COL1A1), and osteocalcin (OCN) by qRT-PCR and Western Blot. The binding of RUNX1 to A2M was initially analyzed through Jaspar website and subsequently verified by dual-luciferase reporter and ChIP assays. Results: Dex-treated BMSCs had low RUNX1 and A2M expression. Dex treatment apparently elevated ROS and LDH levels, diminished cell proliferation rate and SOD, CAT, and Gpx expression, lightened intensity of ALP staining, and declined calcified nodules, ALP activity, and RUNX2, COL1A1, and OCN expression in BMSCs, which was counterweighed by RUNX1 or A2M overexpression. RUNX1 positively targeted A2M. A2M knockdown effectively nullified the ameliorative effects of RUNX1 overexpression on impaired OD and OS injury in Dex-induced BMSCs. Conclusions: Overexpression of RUNX1 attenuated Dex-induced impaired OD and OS injury in BMSCs by promoting A2M transcription.

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APA Style
HE, Q., ZHU, H., FANG, S. (2024). Overexpression of RUNX1 mitigates dexamethasone-induced impairment of osteogenic differentiation and oxidative stress injury in bone marrow mesenchymal stem cells by promoting alpha-2 macroglobulin transcription. BIOCELL, 48(2), 205-216. https://doi.org/10.32604/biocell.2023.045109
Vancouver Style
HE Q, ZHU H, FANG S. Overexpression of RUNX1 mitigates dexamethasone-induced impairment of osteogenic differentiation and oxidative stress injury in bone marrow mesenchymal stem cells by promoting alpha-2 macroglobulin transcription. BIOCELL . 2024;48(2):205-216 https://doi.org/10.32604/biocell.2023.045109
IEEE Style
Q. HE, H. ZHU, and S. FANG "Overexpression of RUNX1 mitigates dexamethasone-induced impairment of osteogenic differentiation and oxidative stress injury in bone marrow mesenchymal stem cells by promoting alpha-2 macroglobulin transcription," BIOCELL , vol. 48, no. 2, pp. 205-216. 2024. https://doi.org/10.32604/biocell.2023.045109



cc This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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