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Long non-coding RNA PVT1, a molecular sponge for miR-149, contributes aberrant metabolic dysfunction and inflammation in IL-1β-simulated osteoarthritic chondrocytes

Osteoarthritis (OA), a common form of degenerative joint disease, is typified by inflammatory response and the loss of cartilage matrix. Long non-coding RNAs (lncRNAs) are emerging as a new player in gene regulation and exert critical roles in diverse physiologic and pathogenic processes including O...

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Autores principales: Zhao, Yangxue, Zhao, Jiang, Guo, Xufeng, She, Jiang, Liu, Yongjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165834/
https://www.ncbi.nlm.nih.gov/pubmed/30126849
http://dx.doi.org/10.1042/BSR20180576
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author Zhao, Yangxue
Zhao, Jiang
Guo, Xufeng
She, Jiang
Liu, Yongjun
author_facet Zhao, Yangxue
Zhao, Jiang
Guo, Xufeng
She, Jiang
Liu, Yongjun
author_sort Zhao, Yangxue
collection PubMed
description Osteoarthritis (OA), a common form of degenerative joint disease, is typified by inflammatory response and the loss of cartilage matrix. Long non-coding RNAs (lncRNAs) are emerging as a new player in gene regulation and exert critical roles in diverse physiologic and pathogenic processes including OA. The lncRNA plasmacytoma variant translocation 1 (PVT1) has been implicated in cancer, diabetes and septic acute kidney injury. Recent research confirmed the elevation of PVT1 in patients with OA. However, its role in the development of OA remains poorly elucidated. In the present study, high expression of PVT1 was observed in cartilage of OA patients and IL-1β-stimulated chondrocytes. Moreover, cessation of PVT1 expression dramatically reversed the inhibition of IL-1β on collagen II and aggrecan expression, but suppressed IL-1β-induced elevation of matrix metalloproteinases (MMPs), including MMP-3, MMP-9 and MMP-13. Simultaneously, PVT1 inhibition also antagonized the production of inflammatory cytokines upon IL-1β stimulation, including prostaglandin E2 (PGE2), NO, IL-6, IL-8 and TNF-α. Further molecular mechanism analysis identified PVT1 as an endogenous sponge RNA that could directly bind to miR-149 and repress its expression and activity. More importantly, miR-149 inhibition reversed the protective roles of PVT1 cessation in attenuating IL-1β-evoked matrix aberrant catabolism and inflammation. Together, this research confirms that lowering PVT1 expression may ameliorate the progression of OA by alleviating cartilage imbalance toward catabolism and inflammatory response, thus supporting a promising therapeutic strategy against OA.
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spelling pubmed-61658342018-10-04 Long non-coding RNA PVT1, a molecular sponge for miR-149, contributes aberrant metabolic dysfunction and inflammation in IL-1β-simulated osteoarthritic chondrocytes Zhao, Yangxue Zhao, Jiang Guo, Xufeng She, Jiang Liu, Yongjun Biosci Rep Research Articles Osteoarthritis (OA), a common form of degenerative joint disease, is typified by inflammatory response and the loss of cartilage matrix. Long non-coding RNAs (lncRNAs) are emerging as a new player in gene regulation and exert critical roles in diverse physiologic and pathogenic processes including OA. The lncRNA plasmacytoma variant translocation 1 (PVT1) has been implicated in cancer, diabetes and septic acute kidney injury. Recent research confirmed the elevation of PVT1 in patients with OA. However, its role in the development of OA remains poorly elucidated. In the present study, high expression of PVT1 was observed in cartilage of OA patients and IL-1β-stimulated chondrocytes. Moreover, cessation of PVT1 expression dramatically reversed the inhibition of IL-1β on collagen II and aggrecan expression, but suppressed IL-1β-induced elevation of matrix metalloproteinases (MMPs), including MMP-3, MMP-9 and MMP-13. Simultaneously, PVT1 inhibition also antagonized the production of inflammatory cytokines upon IL-1β stimulation, including prostaglandin E2 (PGE2), NO, IL-6, IL-8 and TNF-α. Further molecular mechanism analysis identified PVT1 as an endogenous sponge RNA that could directly bind to miR-149 and repress its expression and activity. More importantly, miR-149 inhibition reversed the protective roles of PVT1 cessation in attenuating IL-1β-evoked matrix aberrant catabolism and inflammation. Together, this research confirms that lowering PVT1 expression may ameliorate the progression of OA by alleviating cartilage imbalance toward catabolism and inflammatory response, thus supporting a promising therapeutic strategy against OA. Portland Press Ltd. 2018-09-28 /pmc/articles/PMC6165834/ /pubmed/30126849 http://dx.doi.org/10.1042/BSR20180576 Text en © 2018 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 License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Articles
Zhao, Yangxue
Zhao, Jiang
Guo, Xufeng
She, Jiang
Liu, Yongjun
Long non-coding RNA PVT1, a molecular sponge for miR-149, contributes aberrant metabolic dysfunction and inflammation in IL-1β-simulated osteoarthritic chondrocytes
title Long non-coding RNA PVT1, a molecular sponge for miR-149, contributes aberrant metabolic dysfunction and inflammation in IL-1β-simulated osteoarthritic chondrocytes
title_full Long non-coding RNA PVT1, a molecular sponge for miR-149, contributes aberrant metabolic dysfunction and inflammation in IL-1β-simulated osteoarthritic chondrocytes
title_fullStr Long non-coding RNA PVT1, a molecular sponge for miR-149, contributes aberrant metabolic dysfunction and inflammation in IL-1β-simulated osteoarthritic chondrocytes
title_full_unstemmed Long non-coding RNA PVT1, a molecular sponge for miR-149, contributes aberrant metabolic dysfunction and inflammation in IL-1β-simulated osteoarthritic chondrocytes
title_short Long non-coding RNA PVT1, a molecular sponge for miR-149, contributes aberrant metabolic dysfunction and inflammation in IL-1β-simulated osteoarthritic chondrocytes
title_sort long non-coding rna pvt1, a molecular sponge for mir-149, contributes aberrant metabolic dysfunction and inflammation in il-1β-simulated osteoarthritic chondrocytes
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165834/
https://www.ncbi.nlm.nih.gov/pubmed/30126849
http://dx.doi.org/10.1042/BSR20180576
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