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Glucocorticoid-induced activation of NOX/ROS/NF-κB signaling in MSCs contributes to the development of GONFH

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 (µCT) scanning, histopathological, immunohistochemical, reactive oxygen species...

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Autores principales: Xu, Huihui, Zeng, Qinghe, Zou, Kaiao, Huang, Haipeng, Chen, Jiali, Wang, Pinger, Yuan, Wenhua, Xiao, Luwei, Tong, Peijian, Jin, Hongting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10258081/
https://www.ncbi.nlm.nih.gov/pubmed/37306805
http://dx.doi.org/10.1007/s10495-023-01860-2
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author Xu, Huihui
Zeng, Qinghe
Zou, Kaiao
Huang, Haipeng
Chen, Jiali
Wang, Pinger
Yuan, Wenhua
Xiao, Luwei
Tong, Peijian
Jin, Hongting
author_facet Xu, Huihui
Zeng, Qinghe
Zou, Kaiao
Huang, Haipeng
Chen, Jiali
Wang, Pinger
Yuan, Wenhua
Xiao, Luwei
Tong, Peijian
Jin, Hongting
author_sort Xu, Huihui
collection PubMed
description 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 (µCT) 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 transcription‑quantitative 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-κB 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-κB signaling pathway.
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spelling pubmed-102580812023-06-14 Glucocorticoid-induced activation of NOX/ROS/NF-κB signaling in MSCs contributes to the development of GONFH Xu, Huihui Zeng, Qinghe Zou, Kaiao Huang, Haipeng Chen, Jiali Wang, Pinger Yuan, Wenhua Xiao, Luwei Tong, Peijian Jin, Hongting Apoptosis Article 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 (µCT) 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 transcription‑quantitative 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-κB 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-κB signaling pathway. Springer US 2023-06-12 /pmc/articles/PMC10258081/ /pubmed/37306805 http://dx.doi.org/10.1007/s10495-023-01860-2 Text en © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Article
Xu, Huihui
Zeng, Qinghe
Zou, Kaiao
Huang, Haipeng
Chen, Jiali
Wang, Pinger
Yuan, Wenhua
Xiao, Luwei
Tong, Peijian
Jin, Hongting
Glucocorticoid-induced activation of NOX/ROS/NF-κB signaling in MSCs contributes to the development of GONFH
title Glucocorticoid-induced activation of NOX/ROS/NF-κB signaling in MSCs contributes to the development of GONFH
title_full Glucocorticoid-induced activation of NOX/ROS/NF-κB signaling in MSCs contributes to the development of GONFH
title_fullStr Glucocorticoid-induced activation of NOX/ROS/NF-κB signaling in MSCs contributes to the development of GONFH
title_full_unstemmed Glucocorticoid-induced activation of NOX/ROS/NF-κB signaling in MSCs contributes to the development of GONFH
title_short Glucocorticoid-induced activation of NOX/ROS/NF-κB signaling in MSCs contributes to the development of GONFH
title_sort glucocorticoid-induced activation of nox/ros/nf-κb signaling in mscs contributes to the development of gonfh
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10258081/
https://www.ncbi.nlm.nih.gov/pubmed/37306805
http://dx.doi.org/10.1007/s10495-023-01860-2
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