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CircRREB1 mediates lipid metabolism related senescent phenotypes in chondrocytes through FASN post-translational modifications

Osteoarthritis is a prevalent age-related disease characterized by dysregulation of extracellular matrix metabolism, lipid metabolism, and upregulation of senescence-associated secretory phenotypes. Herein, we clarify that CircRREB1 is highly expressed in secondary generation chondrocytes and its de...

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Autores principales: Gong, Zhe, Zhu, Jinjin, Chen, Junxin, Feng, Fan, Zhang, Haitao, Zhang, Zheyuan, Song, Chenxin, Liang, Kaiyu, Yang, Shuhui, Fan, Shunwu, Fang, Xiangqian, Shen, Shuying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10462713/
https://www.ncbi.nlm.nih.gov/pubmed/37640697
http://dx.doi.org/10.1038/s41467-023-40975-7
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author Gong, Zhe
Zhu, Jinjin
Chen, Junxin
Feng, Fan
Zhang, Haitao
Zhang, Zheyuan
Song, Chenxin
Liang, Kaiyu
Yang, Shuhui
Fan, Shunwu
Fang, Xiangqian
Shen, Shuying
author_facet Gong, Zhe
Zhu, Jinjin
Chen, Junxin
Feng, Fan
Zhang, Haitao
Zhang, Zheyuan
Song, Chenxin
Liang, Kaiyu
Yang, Shuhui
Fan, Shunwu
Fang, Xiangqian
Shen, Shuying
author_sort Gong, Zhe
collection PubMed
description Osteoarthritis is a prevalent age-related disease characterized by dysregulation of extracellular matrix metabolism, lipid metabolism, and upregulation of senescence-associated secretory phenotypes. Herein, we clarify that CircRREB1 is highly expressed in secondary generation chondrocytes and its deficiency can alleviate FASN related senescent phenotypes and osteoarthritis progression. CircRREB1 impedes proteasome-mediated degradation of FASN by inhibiting acetylation-mediated ubiquitination. Meanwhile, CircRREB1 induces RanBP2-mediated SUMOylation of FASN and enhances its protein stability. CircRREB1-FASN axis inhibits FGF18 and FGFR3 mediated PI3K-AKT signal transduction, then increased p21 expression. Intra-articular injection of adenovirus–CircRreb1 reverses the protective effects in CircRreb1 deficiency mice. Further therapeutic interventions could have beneficial effects in identifying CircRREB1 as a potential prognostic and therapeutic target for age-related OA.
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spelling pubmed-104627132023-08-30 CircRREB1 mediates lipid metabolism related senescent phenotypes in chondrocytes through FASN post-translational modifications Gong, Zhe Zhu, Jinjin Chen, Junxin Feng, Fan Zhang, Haitao Zhang, Zheyuan Song, Chenxin Liang, Kaiyu Yang, Shuhui Fan, Shunwu Fang, Xiangqian Shen, Shuying Nat Commun Article Osteoarthritis is a prevalent age-related disease characterized by dysregulation of extracellular matrix metabolism, lipid metabolism, and upregulation of senescence-associated secretory phenotypes. Herein, we clarify that CircRREB1 is highly expressed in secondary generation chondrocytes and its deficiency can alleviate FASN related senescent phenotypes and osteoarthritis progression. CircRREB1 impedes proteasome-mediated degradation of FASN by inhibiting acetylation-mediated ubiquitination. Meanwhile, CircRREB1 induces RanBP2-mediated SUMOylation of FASN and enhances its protein stability. CircRREB1-FASN axis inhibits FGF18 and FGFR3 mediated PI3K-AKT signal transduction, then increased p21 expression. Intra-articular injection of adenovirus–CircRreb1 reverses the protective effects in CircRreb1 deficiency mice. Further therapeutic interventions could have beneficial effects in identifying CircRREB1 as a potential prognostic and therapeutic target for age-related OA. Nature Publishing Group UK 2023-08-28 /pmc/articles/PMC10462713/ /pubmed/37640697 http://dx.doi.org/10.1038/s41467-023-40975-7 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
Gong, Zhe
Zhu, Jinjin
Chen, Junxin
Feng, Fan
Zhang, Haitao
Zhang, Zheyuan
Song, Chenxin
Liang, Kaiyu
Yang, Shuhui
Fan, Shunwu
Fang, Xiangqian
Shen, Shuying
CircRREB1 mediates lipid metabolism related senescent phenotypes in chondrocytes through FASN post-translational modifications
title CircRREB1 mediates lipid metabolism related senescent phenotypes in chondrocytes through FASN post-translational modifications
title_full CircRREB1 mediates lipid metabolism related senescent phenotypes in chondrocytes through FASN post-translational modifications
title_fullStr CircRREB1 mediates lipid metabolism related senescent phenotypes in chondrocytes through FASN post-translational modifications
title_full_unstemmed CircRREB1 mediates lipid metabolism related senescent phenotypes in chondrocytes through FASN post-translational modifications
title_short CircRREB1 mediates lipid metabolism related senescent phenotypes in chondrocytes through FASN post-translational modifications
title_sort circrreb1 mediates lipid metabolism related senescent phenotypes in chondrocytes through fasn post-translational modifications
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10462713/
https://www.ncbi.nlm.nih.gov/pubmed/37640697
http://dx.doi.org/10.1038/s41467-023-40975-7
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