학술논문
Glucocorticoid-induced activation of NOX/ROS/NF-[kappa]B signaling in MSCs contributes to the development of GONFH
Article
Article
Document Type
Academic Journal
Author
Source
Apoptosis - An International Journal on Programmed Cell Death. October 2023, Vol. 28 Issue 9-10, p1332, 14 p.
Subject
Language
English
ISSN
1360-8185
Abstract
Author(s): Huihui Xu [sup.1] [sup.2] [sup.3], Qinghe Zeng [sup.1] [sup.2] [sup.3], Kaiao Zou [sup.1] [sup.2] [sup.3], Haipeng Huang [sup.1] [sup.2] [sup.3], Jiali Chen [sup.1] [sup.3], Pinger Wang [sup.1] [sup.3], Wenhua [...]
Background: This study aimed to investigate the pathogenic factors of glucocorticoids (GCs)-induced osteonecrosis of the femoral head (GONFH) and its underlying pathogenesis in vivo and in vitro. Methods: Radiographical ([micro]CT) scanning, histopathological, immunohistochemical, reactive oxygen species (ROS) and tunel staining were conducted on GONFH patients and rats. ROS, tunel, flow cytometry, alkaline phosphatase, Oil red O staining, reverse transcriptionâquantitative PCR and western blotting were applied to elucidate the exact pathogenesis mechanism. Results: Clinical and animal studies demonstrated increased levels of ROS, aggravated oxidative stress (OS) microenvironment, augmented apoptosis and imbalance in osteogenic/lipogenic in the GONFH group compared to the control group. The fate of mesenchymal stem cells (MSCs) directed by GCs is a crucial factor in determining GONFH. In vitro studies further revealed that GCs promote excessive ROS production through the expression of NOX family proteins, leading to a deterioration of the OS microenvironment in MSCs, ultimately resulting in apoptosis and imbalance in osteogenic/lipogenic differentiation. Furthermore, our results confirmed that the NOX inhibitor-diphenyleneiodonium chloride and the NF-[kappa]B inhibitor-BAY 11-7082 ameliorated apoptosis and osteogenic/lipogenic differentiation imbalance of MSCs induced by an excess of GCs. Conclusion: We demonstrated for the first time that the aggravation of the OS microenvironment in MSCs caused by high doses of GCs leading to apoptosis and differentiation imbalance is a crucial factor in the pathogenesis of GONFH, mediated through activating the NOX/ROS/NF-[kappa]B signaling pathway.
Background: This study aimed to investigate the pathogenic factors of glucocorticoids (GCs)-induced osteonecrosis of the femoral head (GONFH) and its underlying pathogenesis in vivo and in vitro. Methods: Radiographical ([micro]CT) scanning, histopathological, immunohistochemical, reactive oxygen species (ROS) and tunel staining were conducted on GONFH patients and rats. ROS, tunel, flow cytometry, alkaline phosphatase, Oil red O staining, reverse transcriptionâquantitative PCR and western blotting were applied to elucidate the exact pathogenesis mechanism. Results: Clinical and animal studies demonstrated increased levels of ROS, aggravated oxidative stress (OS) microenvironment, augmented apoptosis and imbalance in osteogenic/lipogenic in the GONFH group compared to the control group. The fate of mesenchymal stem cells (MSCs) directed by GCs is a crucial factor in determining GONFH. In vitro studies further revealed that GCs promote excessive ROS production through the expression of NOX family proteins, leading to a deterioration of the OS microenvironment in MSCs, ultimately resulting in apoptosis and imbalance in osteogenic/lipogenic differentiation. Furthermore, our results confirmed that the NOX inhibitor-diphenyleneiodonium chloride and the NF-[kappa]B inhibitor-BAY 11-7082 ameliorated apoptosis and osteogenic/lipogenic differentiation imbalance of MSCs induced by an excess of GCs. Conclusion: We demonstrated for the first time that the aggravation of the OS microenvironment in MSCs caused by high doses of GCs leading to apoptosis and differentiation imbalance is a crucial factor in the pathogenesis of GONFH, mediated through activating the NOX/ROS/NF-[kappa]B signaling pathway.