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MicroRNA-33 suppresses CCL2 expression in chondrocytes

CCL2-mediated macrophage infiltration in articular tissues plays a pivotal role in the development of the osteoarthritis (OA). miRNAs regulate the onset and progression of diseases via controlling the expression of a series of genes. How the CCL2 gene was regulated by miRNAs was still not fully eluc...

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Autores principales: Wei, Meng, Xie, Qingyun, Zhu, Jun, Wang, Tao, Zhang, Fan, Cheng, Yue, Guo, Dongyang, Wang, Ying, Mo, Liweng, Wang, Shuai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4859085/
https://www.ncbi.nlm.nih.gov/pubmed/27129293
http://dx.doi.org/10.1042/BSR20160068
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author Wei, Meng
Xie, Qingyun
Zhu, Jun
Wang, Tao
Zhang, Fan
Cheng, Yue
Guo, Dongyang
Wang, Ying
Mo, Liweng
Wang, Shuai
author_facet Wei, Meng
Xie, Qingyun
Zhu, Jun
Wang, Tao
Zhang, Fan
Cheng, Yue
Guo, Dongyang
Wang, Ying
Mo, Liweng
Wang, Shuai
author_sort Wei, Meng
collection PubMed
description CCL2-mediated macrophage infiltration in articular tissues plays a pivotal role in the development of the osteoarthritis (OA). miRNAs regulate the onset and progression of diseases via controlling the expression of a series of genes. How the CCL2 gene was regulated by miRNAs was still not fully elucidated. In the present study, we demonstrated that the binding sites of miR-33 in the 3′UTR of CCL2 gene were conserved in human, mouse and rat species. By performing gain- or loss-of-function studies, we verified that miR-33 suppressed CCL2 expression in the mRNA and protein levels. We also found that miR-33 suppressed the CCL2 levels in the supernatant of cultured primary mouse chondrocytes. With reporter gene assay, we demonstrated that miR-33 targeted at AAUGCA in the 3′UTR of CCL2 gene. In transwell migration assays, we demonstrated that the conditional medium (CM) from miR-33 deficient chondrocytes potentiated the monocyte chemotaxis in a CCL2 dependent manner. Finally, we demonstrated that the level of miR-33 was decreased, whereas the CCL2 level was increased in the articular cartilage from the OA patients compared with the control group. In summary, we identified miR-33 as a novel suppressor of CCL2 in chondrocytes. The miR-33/CCL2 axis in chondrocytes regulates monocyte chemotaxis, providing a potential mechanism of macrophage infiltration in OA.
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spelling pubmed-48590852016-06-01 MicroRNA-33 suppresses CCL2 expression in chondrocytes Wei, Meng Xie, Qingyun Zhu, Jun Wang, Tao Zhang, Fan Cheng, Yue Guo, Dongyang Wang, Ying Mo, Liweng Wang, Shuai Biosci Rep Original Papers CCL2-mediated macrophage infiltration in articular tissues plays a pivotal role in the development of the osteoarthritis (OA). miRNAs regulate the onset and progression of diseases via controlling the expression of a series of genes. How the CCL2 gene was regulated by miRNAs was still not fully elucidated. In the present study, we demonstrated that the binding sites of miR-33 in the 3′UTR of CCL2 gene were conserved in human, mouse and rat species. By performing gain- or loss-of-function studies, we verified that miR-33 suppressed CCL2 expression in the mRNA and protein levels. We also found that miR-33 suppressed the CCL2 levels in the supernatant of cultured primary mouse chondrocytes. With reporter gene assay, we demonstrated that miR-33 targeted at AAUGCA in the 3′UTR of CCL2 gene. In transwell migration assays, we demonstrated that the conditional medium (CM) from miR-33 deficient chondrocytes potentiated the monocyte chemotaxis in a CCL2 dependent manner. Finally, we demonstrated that the level of miR-33 was decreased, whereas the CCL2 level was increased in the articular cartilage from the OA patients compared with the control group. In summary, we identified miR-33 as a novel suppressor of CCL2 in chondrocytes. The miR-33/CCL2 axis in chondrocytes regulates monocyte chemotaxis, providing a potential mechanism of macrophage infiltration in OA. Portland Press Ltd. 2016-05-06 /pmc/articles/PMC4859085/ /pubmed/27129293 http://dx.doi.org/10.1042/BSR20160068 Text en © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution Licence 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Papers
Wei, Meng
Xie, Qingyun
Zhu, Jun
Wang, Tao
Zhang, Fan
Cheng, Yue
Guo, Dongyang
Wang, Ying
Mo, Liweng
Wang, Shuai
MicroRNA-33 suppresses CCL2 expression in chondrocytes
title MicroRNA-33 suppresses CCL2 expression in chondrocytes
title_full MicroRNA-33 suppresses CCL2 expression in chondrocytes
title_fullStr MicroRNA-33 suppresses CCL2 expression in chondrocytes
title_full_unstemmed MicroRNA-33 suppresses CCL2 expression in chondrocytes
title_short MicroRNA-33 suppresses CCL2 expression in chondrocytes
title_sort microrna-33 suppresses ccl2 expression in chondrocytes
topic Original Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4859085/
https://www.ncbi.nlm.nih.gov/pubmed/27129293
http://dx.doi.org/10.1042/BSR20160068
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