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Salubrinal Alleviates Collagen-Induced Arthritis through Promoting P65 Degradation in Osteoclastogenesis

Rheumatoid arthritis (RA) is a complex systemic autoimmune disorder that primarily involves joints, further affects the life quality of patients, and has increased mortality. The pathogenesis of RA involves multiple pathways, resulting in some patients showing resistance to the existing drugs. Salub...

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Detalles Bibliográficos
Autores principales: Wang, Ziyu, Li, Zijian, Wang, Guojue, Sun, Ying, Yuan, Yuanyang, Nie, Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037325/
https://www.ncbi.nlm.nih.gov/pubmed/33800699
http://dx.doi.org/10.3390/ijms22073501
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author Wang, Ziyu
Li, Zijian
Wang, Guojue
Sun, Ying
Yuan, Yuanyang
Nie, Hong
author_facet Wang, Ziyu
Li, Zijian
Wang, Guojue
Sun, Ying
Yuan, Yuanyang
Nie, Hong
author_sort Wang, Ziyu
collection PubMed
description Rheumatoid arthritis (RA) is a complex systemic autoimmune disorder that primarily involves joints, further affects the life quality of patients, and has increased mortality. The pathogenesis of RA involves multiple pathways, resulting in some patients showing resistance to the existing drugs. Salubrinal is a small molecule compound that has recently been shown to exert multiple beneficial effects on bone tissue. However, the effect of Salubrinal in RA has not been clearly confirmed. Hence, we induced collagen-induced arthritis (CIA) in DBA/1J mice and found that Salubrinal treatment decreased the clinical score of CIA mice, inhibiting joint damage and bone destruction. Furthermore, Salubrinal treatment downregulated osteoclast number in knee joint of CIA in mice, and suppressed bone marrow-derived osteoclast formation and function, downregulated osteoclast-related gene expression. Moreover, Salubrinal treatment inhibited RANKL-induced NF-κB signaling pathway, and promoted P65 degradation through the ubiquitin-proteasome system, further restrained RANKL-induced osteoclastogenesis. This study explains the mechanism by which Salubrinal ameliorates arthritis of CIA in mice, indicating that Salubrinal may be a potential drug for RA, and expands the potential uses of Salubrinal in the treatment of bone destruction-related diseases.
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spelling pubmed-80373252021-04-12 Salubrinal Alleviates Collagen-Induced Arthritis through Promoting P65 Degradation in Osteoclastogenesis Wang, Ziyu Li, Zijian Wang, Guojue Sun, Ying Yuan, Yuanyang Nie, Hong Int J Mol Sci Article Rheumatoid arthritis (RA) is a complex systemic autoimmune disorder that primarily involves joints, further affects the life quality of patients, and has increased mortality. The pathogenesis of RA involves multiple pathways, resulting in some patients showing resistance to the existing drugs. Salubrinal is a small molecule compound that has recently been shown to exert multiple beneficial effects on bone tissue. However, the effect of Salubrinal in RA has not been clearly confirmed. Hence, we induced collagen-induced arthritis (CIA) in DBA/1J mice and found that Salubrinal treatment decreased the clinical score of CIA mice, inhibiting joint damage and bone destruction. Furthermore, Salubrinal treatment downregulated osteoclast number in knee joint of CIA in mice, and suppressed bone marrow-derived osteoclast formation and function, downregulated osteoclast-related gene expression. Moreover, Salubrinal treatment inhibited RANKL-induced NF-κB signaling pathway, and promoted P65 degradation through the ubiquitin-proteasome system, further restrained RANKL-induced osteoclastogenesis. This study explains the mechanism by which Salubrinal ameliorates arthritis of CIA in mice, indicating that Salubrinal may be a potential drug for RA, and expands the potential uses of Salubrinal in the treatment of bone destruction-related diseases. MDPI 2021-03-28 /pmc/articles/PMC8037325/ /pubmed/33800699 http://dx.doi.org/10.3390/ijms22073501 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Wang, Ziyu
Li, Zijian
Wang, Guojue
Sun, Ying
Yuan, Yuanyang
Nie, Hong
Salubrinal Alleviates Collagen-Induced Arthritis through Promoting P65 Degradation in Osteoclastogenesis
title Salubrinal Alleviates Collagen-Induced Arthritis through Promoting P65 Degradation in Osteoclastogenesis
title_full Salubrinal Alleviates Collagen-Induced Arthritis through Promoting P65 Degradation in Osteoclastogenesis
title_fullStr Salubrinal Alleviates Collagen-Induced Arthritis through Promoting P65 Degradation in Osteoclastogenesis
title_full_unstemmed Salubrinal Alleviates Collagen-Induced Arthritis through Promoting P65 Degradation in Osteoclastogenesis
title_short Salubrinal Alleviates Collagen-Induced Arthritis through Promoting P65 Degradation in Osteoclastogenesis
title_sort salubrinal alleviates collagen-induced arthritis through promoting p65 degradation in osteoclastogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037325/
https://www.ncbi.nlm.nih.gov/pubmed/33800699
http://dx.doi.org/10.3390/ijms22073501
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