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CircSLC7A2 protects against osteoarthritis through inhibition of the miR‐4498/TIMP3 axis
OBJECTIVES: Circular RNAs (circRNAs) are noncoding RNAs that compete against other endogenous RNA species, such as microRNAs, and have been implicated in many diseases. In this study, we investigated the role of a new circRNA (circSLC7A2) in osteoarthritis (OA). MATERIALS AND METHODS: The relative e...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168424/ https://www.ncbi.nlm.nih.gov/pubmed/33960555 http://dx.doi.org/10.1111/cpr.13047 |
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author | Ni, Weiyu Jiang, Chao Wu, Yizheng Zhang, Haitao Wang, Lili Yik, Jasper H.N. Haudenschild, Dominik R. Fan, Shunwu Shen, Shuying Hu, Ziang |
author_facet | Ni, Weiyu Jiang, Chao Wu, Yizheng Zhang, Haitao Wang, Lili Yik, Jasper H.N. Haudenschild, Dominik R. Fan, Shunwu Shen, Shuying Hu, Ziang |
author_sort | Ni, Weiyu |
collection | PubMed |
description | OBJECTIVES: Circular RNAs (circRNAs) are noncoding RNAs that compete against other endogenous RNA species, such as microRNAs, and have been implicated in many diseases. In this study, we investigated the role of a new circRNA (circSLC7A2) in osteoarthritis (OA). MATERIALS AND METHODS: The relative expression of circSLC7A2 was significantly lower in OA tissues than it was in matched controls, as shown by real‐time quantitative polymerase chain reaction (RT‐qPCR). Western blotting, RT‐qPCR and immunofluorescence experiments were employed to evaluate the roles of circSLC7A2, miR‐4498 and TIMP3. The in vivo role and mechanism of circSLC7A2 were also conformed in a mouse model. RESULTS: circSLC7A2 was decreased in OA model and the circularization of circSLC7A2 was regulated by FUS. Loss of circSLC7A2 reduced the sponge of miR‐4498 and further inhibited the expression of TIMP3, subsequently leading to an inflammatory response. We further determined that miR‐4498 inhibitor reversed circSLC7A2‐knockdown‐induced OA phenotypes. Intra‐articular injection of circSLC7A2 alleviated in vivo OA progression in a mouse model of anterior cruciate ligament transection (ACLT). CONCLUSIONS: The circSLC7A2/miR‐4498/TIMP3 axis of chondrocytes catabolism and anabolism plays a critical role in OA development. Our results suggest that circSLC7A2 may serve as a new therapeutic target for osteoarthritis. |
format | Online Article Text |
id | pubmed-8168424 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81684242021-06-05 CircSLC7A2 protects against osteoarthritis through inhibition of the miR‐4498/TIMP3 axis Ni, Weiyu Jiang, Chao Wu, Yizheng Zhang, Haitao Wang, Lili Yik, Jasper H.N. Haudenschild, Dominik R. Fan, Shunwu Shen, Shuying Hu, Ziang Cell Prolif Original Articles OBJECTIVES: Circular RNAs (circRNAs) are noncoding RNAs that compete against other endogenous RNA species, such as microRNAs, and have been implicated in many diseases. In this study, we investigated the role of a new circRNA (circSLC7A2) in osteoarthritis (OA). MATERIALS AND METHODS: The relative expression of circSLC7A2 was significantly lower in OA tissues than it was in matched controls, as shown by real‐time quantitative polymerase chain reaction (RT‐qPCR). Western blotting, RT‐qPCR and immunofluorescence experiments were employed to evaluate the roles of circSLC7A2, miR‐4498 and TIMP3. The in vivo role and mechanism of circSLC7A2 were also conformed in a mouse model. RESULTS: circSLC7A2 was decreased in OA model and the circularization of circSLC7A2 was regulated by FUS. Loss of circSLC7A2 reduced the sponge of miR‐4498 and further inhibited the expression of TIMP3, subsequently leading to an inflammatory response. We further determined that miR‐4498 inhibitor reversed circSLC7A2‐knockdown‐induced OA phenotypes. Intra‐articular injection of circSLC7A2 alleviated in vivo OA progression in a mouse model of anterior cruciate ligament transection (ACLT). CONCLUSIONS: The circSLC7A2/miR‐4498/TIMP3 axis of chondrocytes catabolism and anabolism plays a critical role in OA development. Our results suggest that circSLC7A2 may serve as a new therapeutic target for osteoarthritis. John Wiley and Sons Inc. 2021-05-07 /pmc/articles/PMC8168424/ /pubmed/33960555 http://dx.doi.org/10.1111/cpr.13047 Text en © 2021 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Ni, Weiyu Jiang, Chao Wu, Yizheng Zhang, Haitao Wang, Lili Yik, Jasper H.N. Haudenschild, Dominik R. Fan, Shunwu Shen, Shuying Hu, Ziang CircSLC7A2 protects against osteoarthritis through inhibition of the miR‐4498/TIMP3 axis |
title | CircSLC7A2 protects against osteoarthritis through inhibition of the miR‐4498/TIMP3 axis |
title_full | CircSLC7A2 protects against osteoarthritis through inhibition of the miR‐4498/TIMP3 axis |
title_fullStr | CircSLC7A2 protects against osteoarthritis through inhibition of the miR‐4498/TIMP3 axis |
title_full_unstemmed | CircSLC7A2 protects against osteoarthritis through inhibition of the miR‐4498/TIMP3 axis |
title_short | CircSLC7A2 protects against osteoarthritis through inhibition of the miR‐4498/TIMP3 axis |
title_sort | circslc7a2 protects against osteoarthritis through inhibition of the mir‐4498/timp3 axis |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168424/ https://www.ncbi.nlm.nih.gov/pubmed/33960555 http://dx.doi.org/10.1111/cpr.13047 |
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