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NR1D1 modulates synovial inflammation and bone destruction in rheumatoid arthritis
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial hyperplasia, pannus formation, and cartilage and bone destruction. Nuclear receptor subfamily 1 group D member 1 (NR1D1) functions as a transcriptional repressor and plays a vital role in inflammatory reactions. Howe...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028921/ https://www.ncbi.nlm.nih.gov/pubmed/32071294 http://dx.doi.org/10.1038/s41419-020-2314-6 |
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author | Liu, Hui Zhu, Yuanli Gao, Yutong Qi, Dahu Zhao, Liming Zhao, Libo Liu, Changyu Tao, Tenghui Zhou, Chuankun Sun, Xuying Guo, Fengjing Xiao, Jun |
author_facet | Liu, Hui Zhu, Yuanli Gao, Yutong Qi, Dahu Zhao, Liming Zhao, Libo Liu, Changyu Tao, Tenghui Zhou, Chuankun Sun, Xuying Guo, Fengjing Xiao, Jun |
author_sort | Liu, Hui |
collection | PubMed |
description | Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial hyperplasia, pannus formation, and cartilage and bone destruction. Nuclear receptor subfamily 1 group D member 1 (NR1D1) functions as a transcriptional repressor and plays a vital role in inflammatory reactions. However, whether NR1D1 is involved in synovial inflammation and joint destruction during the pathogenesis of RA is unknown. In this study, we found that NR1D1 expression was increased in synovial tissues from patients with RA and decreased in RA Fibroblast-like synoviocytes (FLSs) stimulated with IL-1β in vitro. We showed that NR1D1 activation decreased the expression of proinflammatory cytokines and matrix metalloproteinases (MMPs), while NR1D1 silencing exerted the opposite effect. Furthermore, NR1D1 activation reduced reactive oxygen species (ROS) generation and increased the production of nuclear transcription factor E2-related factor 2 (Nrf2)-associated enzymes. Mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) pathways were blocked by the NR1D1 agonist SR9009 but activated by NR1D1 silencing. NR1D1 activation also inhibited M1 macrophage polarization and suppressed osteoclastogenesis and osteoclast-related genes expression. Treatment with NR1D1 agonist SR9009 in collagen-induced arthritis (CIA) mouse significantly suppressed the hyperplasia of synovial, infiltration of inflammatory cell and destruction of cartilage and bone. Our findings demonstrate an important role for NR1D1 in RA and suggest its therapeutic potential. |
format | Online Article Text |
id | pubmed-7028921 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-70289212020-02-25 NR1D1 modulates synovial inflammation and bone destruction in rheumatoid arthritis Liu, Hui Zhu, Yuanli Gao, Yutong Qi, Dahu Zhao, Liming Zhao, Libo Liu, Changyu Tao, Tenghui Zhou, Chuankun Sun, Xuying Guo, Fengjing Xiao, Jun Cell Death Dis Article Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial hyperplasia, pannus formation, and cartilage and bone destruction. Nuclear receptor subfamily 1 group D member 1 (NR1D1) functions as a transcriptional repressor and plays a vital role in inflammatory reactions. However, whether NR1D1 is involved in synovial inflammation and joint destruction during the pathogenesis of RA is unknown. In this study, we found that NR1D1 expression was increased in synovial tissues from patients with RA and decreased in RA Fibroblast-like synoviocytes (FLSs) stimulated with IL-1β in vitro. We showed that NR1D1 activation decreased the expression of proinflammatory cytokines and matrix metalloproteinases (MMPs), while NR1D1 silencing exerted the opposite effect. Furthermore, NR1D1 activation reduced reactive oxygen species (ROS) generation and increased the production of nuclear transcription factor E2-related factor 2 (Nrf2)-associated enzymes. Mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) pathways were blocked by the NR1D1 agonist SR9009 but activated by NR1D1 silencing. NR1D1 activation also inhibited M1 macrophage polarization and suppressed osteoclastogenesis and osteoclast-related genes expression. Treatment with NR1D1 agonist SR9009 in collagen-induced arthritis (CIA) mouse significantly suppressed the hyperplasia of synovial, infiltration of inflammatory cell and destruction of cartilage and bone. Our findings demonstrate an important role for NR1D1 in RA and suggest its therapeutic potential. Nature Publishing Group UK 2020-02-18 /pmc/articles/PMC7028921/ /pubmed/32071294 http://dx.doi.org/10.1038/s41419-020-2314-6 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Liu, Hui Zhu, Yuanli Gao, Yutong Qi, Dahu Zhao, Liming Zhao, Libo Liu, Changyu Tao, Tenghui Zhou, Chuankun Sun, Xuying Guo, Fengjing Xiao, Jun NR1D1 modulates synovial inflammation and bone destruction in rheumatoid arthritis |
title | NR1D1 modulates synovial inflammation and bone destruction in rheumatoid arthritis |
title_full | NR1D1 modulates synovial inflammation and bone destruction in rheumatoid arthritis |
title_fullStr | NR1D1 modulates synovial inflammation and bone destruction in rheumatoid arthritis |
title_full_unstemmed | NR1D1 modulates synovial inflammation and bone destruction in rheumatoid arthritis |
title_short | NR1D1 modulates synovial inflammation and bone destruction in rheumatoid arthritis |
title_sort | nr1d1 modulates synovial inflammation and bone destruction in rheumatoid arthritis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028921/ https://www.ncbi.nlm.nih.gov/pubmed/32071294 http://dx.doi.org/10.1038/s41419-020-2314-6 |
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