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Cardamonin protects against iron overload induced arthritis by attenuating ROS production and NLRP3 inflammasome activation via the SIRT1/p38MAPK signaling pathway

Iron homeostasis plays an essential role in joint health, while iron overload can cause damage and death of cartilage cells. Cardamonin (CAR) is a substance found in the fruit of the chasteberry plant and has anti-inflammatory and anti-tumor activities. We first administered iron dextran (500 mg/kg)...

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Autores principales: Li, Shaocong, He, Qi, Chen, Baihao, Zeng, Jiaxu, Dou, Xiangyun, Pan, Zhaofeng, Xiao, Jiacong, Li, Miao, Wang, Fanchen, Chen, Chuyi, Lin, Yuewei, Wang, Xintian, Wang, Haibin, Chen, Jianfa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10447427/
https://www.ncbi.nlm.nih.gov/pubmed/37612419
http://dx.doi.org/10.1038/s41598-023-40930-y
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author Li, Shaocong
He, Qi
Chen, Baihao
Zeng, Jiaxu
Dou, Xiangyun
Pan, Zhaofeng
Xiao, Jiacong
Li, Miao
Wang, Fanchen
Chen, Chuyi
Lin, Yuewei
Wang, Xintian
Wang, Haibin
Chen, Jianfa
author_facet Li, Shaocong
He, Qi
Chen, Baihao
Zeng, Jiaxu
Dou, Xiangyun
Pan, Zhaofeng
Xiao, Jiacong
Li, Miao
Wang, Fanchen
Chen, Chuyi
Lin, Yuewei
Wang, Xintian
Wang, Haibin
Chen, Jianfa
author_sort Li, Shaocong
collection PubMed
description Iron homeostasis plays an essential role in joint health, while iron overload can cause damage and death of cartilage cells. Cardamonin (CAR) is a substance found in the fruit of the chasteberry plant and has anti-inflammatory and anti-tumor activities. We first administered iron dextran (500 mg/kg) intraperitoneally to establish an iron overload mouse model and surgically induced osteoarthritis. The extent of OA and iron deposition were assessed using Micro-ct, Safranin-O/fast green staining, H&E staining, and Prussian Blue 10 weeks later. We administered primary chondrocytes with Ferric Ammonium Citrate (FAC) to evaluate the chondrocyte changes. Chondrocytes were identified in vitro by toluidine blue staining, and chondrocyte viability was evaluated by CCK-8. The rate of apoptosis was determined by Annexin V-FITC/PI assay. The mechanism of action of CAR was verified by adding the SIRT1 inhibitor EX527, and the expression of SIRT1 and MAPK signaling pathways was detected by Western blot. Iron overload also promoted chondrocyte apoptosis, a process that was reversed by CAR. In addition, CAR reduced NLRP3 inflammasome production via the SIRT1-MAPK pathway, and the SIRT1 inhibitor EX527 inhibited the treatment of OA by CAR.CAR inhibited cartilage degeneration induced by iron overload both in vivo and in vitro. Besides, our study showed that iron overload not only inhibited type II collagen expression but also induced MMP expression by catalyzing the generation of NLRP3 inflammasome. Our results suggest that CAR can treat KOA by promoting SIRT1 expression and inhibiting p38MAPK pathway expression to reduce the production of NLRP3 inflammasome vesicles.
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spelling pubmed-104474272023-08-25 Cardamonin protects against iron overload induced arthritis by attenuating ROS production and NLRP3 inflammasome activation via the SIRT1/p38MAPK signaling pathway Li, Shaocong He, Qi Chen, Baihao Zeng, Jiaxu Dou, Xiangyun Pan, Zhaofeng Xiao, Jiacong Li, Miao Wang, Fanchen Chen, Chuyi Lin, Yuewei Wang, Xintian Wang, Haibin Chen, Jianfa Sci Rep Article Iron homeostasis plays an essential role in joint health, while iron overload can cause damage and death of cartilage cells. Cardamonin (CAR) is a substance found in the fruit of the chasteberry plant and has anti-inflammatory and anti-tumor activities. We first administered iron dextran (500 mg/kg) intraperitoneally to establish an iron overload mouse model and surgically induced osteoarthritis. The extent of OA and iron deposition were assessed using Micro-ct, Safranin-O/fast green staining, H&E staining, and Prussian Blue 10 weeks later. We administered primary chondrocytes with Ferric Ammonium Citrate (FAC) to evaluate the chondrocyte changes. Chondrocytes were identified in vitro by toluidine blue staining, and chondrocyte viability was evaluated by CCK-8. The rate of apoptosis was determined by Annexin V-FITC/PI assay. The mechanism of action of CAR was verified by adding the SIRT1 inhibitor EX527, and the expression of SIRT1 and MAPK signaling pathways was detected by Western blot. Iron overload also promoted chondrocyte apoptosis, a process that was reversed by CAR. In addition, CAR reduced NLRP3 inflammasome production via the SIRT1-MAPK pathway, and the SIRT1 inhibitor EX527 inhibited the treatment of OA by CAR.CAR inhibited cartilage degeneration induced by iron overload both in vivo and in vitro. Besides, our study showed that iron overload not only inhibited type II collagen expression but also induced MMP expression by catalyzing the generation of NLRP3 inflammasome. Our results suggest that CAR can treat KOA by promoting SIRT1 expression and inhibiting p38MAPK pathway expression to reduce the production of NLRP3 inflammasome vesicles. Nature Publishing Group UK 2023-08-23 /pmc/articles/PMC10447427/ /pubmed/37612419 http://dx.doi.org/10.1038/s41598-023-40930-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Li, Shaocong
He, Qi
Chen, Baihao
Zeng, Jiaxu
Dou, Xiangyun
Pan, Zhaofeng
Xiao, Jiacong
Li, Miao
Wang, Fanchen
Chen, Chuyi
Lin, Yuewei
Wang, Xintian
Wang, Haibin
Chen, Jianfa
Cardamonin protects against iron overload induced arthritis by attenuating ROS production and NLRP3 inflammasome activation via the SIRT1/p38MAPK signaling pathway
title Cardamonin protects against iron overload induced arthritis by attenuating ROS production and NLRP3 inflammasome activation via the SIRT1/p38MAPK signaling pathway
title_full Cardamonin protects against iron overload induced arthritis by attenuating ROS production and NLRP3 inflammasome activation via the SIRT1/p38MAPK signaling pathway
title_fullStr Cardamonin protects against iron overload induced arthritis by attenuating ROS production and NLRP3 inflammasome activation via the SIRT1/p38MAPK signaling pathway
title_full_unstemmed Cardamonin protects against iron overload induced arthritis by attenuating ROS production and NLRP3 inflammasome activation via the SIRT1/p38MAPK signaling pathway
title_short Cardamonin protects against iron overload induced arthritis by attenuating ROS production and NLRP3 inflammasome activation via the SIRT1/p38MAPK signaling pathway
title_sort cardamonin protects against iron overload induced arthritis by attenuating ros production and nlrp3 inflammasome activation via the sirt1/p38mapk signaling pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10447427/
https://www.ncbi.nlm.nih.gov/pubmed/37612419
http://dx.doi.org/10.1038/s41598-023-40930-y
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