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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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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. |
format | Online Article Text |
id | pubmed-10462713 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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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