Research Paper Volume 15, Issue 6 pp 2033—2045
Epimedin C protects dexamethasone-induced osteoblasts through NRF1/RhoA pathway
- 1 Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan, Hubei 430022, China
- 2 College of Life Science Gannan Normal University, Jiangxi 341000, China
- 3 Key Laboratory of South China Agricultural Plant Molecular Analysis and Genetic Improvement, Provincial Key Laboratory of Digital Botanical Garden and Public Science, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, China
- 4 Wuhan Red Cross Hospital, Wuhan, Hubei 430000, China
- 5 Medical Sciences Building MA202, School of Medicine, University of Missouri, Columbia, MO 65212, USA
Received: December 4, 2022 Accepted: February 27, 2023 Published: March 14, 2023
https://doi.org/10.18632/aging.204588How to Cite
Copyright: © 2023 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Osteoporosis (OP) is a metabolic bone disease that leads to decrease of bone strength and increase bone brittle and fracture. Dexamethasone (DXMS) usage is a common risk factor of OP. In present study, we found that the Epimedin C protect the DXMS-induced OP, Ras Homolog Family Member A transforming protein (RhoA) was increased in osteoblasts (OBs) and OP models. We further revealed that Nrf1 is a transcription factor that responds to Epimedin C and DXMS in modulating RhoA promoter. The results collectively demonstrate that Epimedin C functions as a positive modifier of RhoA via alteration of Nrf1 transcriptional activity on RhoA promoter, thereby, protecting OBs against OP. Our work is the first study identifying the Epimedin C function in balancing the OBs in OP model via Nrf1-RhoA.
Abbreviations
RhoA: Ras Homolog Family Member A transforming protein; NFE2L1: Nuclear factor erythroid derived 2-related factor 1; CNC: cap ‘n’ collar; DMEM: Dulbecco’s modified eagle medium; EMSA: Electrophoretic mobility shift assay; DLR: Dual-luciferase reporter; CRISPR: Clustered Regularly Interspaced Short Palindromic Repeats; OPG: osteoclastogenesis inhibitory factor; GTPases: Guanosine-5′-triphosphate-ase; CREB: cAMP response element-binding protein; GDP-bound: guanosine diphosphate-bound; WT: wild type; LC-MS: liquid chromatography–mass spectrometry; MS/MS: tandem mass spectrometry; TOF-MS: Time-of-flight mass spectrometry; TIMS: Thermal Ionization Mass Spectrometer.