CircPan3 Promotes the Ghrelin System and Chondrocyte Autophagy by Sponging miR-667-5p During Rat Osteoarthritis Pathogenesis

This study aimed to investigate the potential roles of circRNAs in regulating osteoarthritis (OA)-related ghrelin synthesis, autophagy induction, and the relevant molecular mechanisms. Results showed that Col2a1, Acan, ghrelin, and autophagy-related markers expression were downregulated, while matri...

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Autores principales:	Jing Zeng, Zhenzhen Zhang, Qing Liao, Qijin Lu, Jiemei Liu, Lixia Yuan, Gang Liu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	circPAN3 miR-667-5p ghrelin chondrocyte autophagy osteoarthritis Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/74de9082050549e39b83a4c679af6448
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spelling	oai:doaj.org-article:74de9082050549e39b83a4c679af64482021-11-19T07:49:49ZCircPan3 Promotes the Ghrelin System and Chondrocyte Autophagy by Sponging miR-667-5p During Rat Osteoarthritis Pathogenesis2296-634X10.3389/fcell.2021.719898https://doaj.org/article/74de9082050549e39b83a4c679af64482021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.719898/fullhttps://doaj.org/toc/2296-634XThis study aimed to investigate the potential roles of circRNAs in regulating osteoarthritis (OA)-related ghrelin synthesis, autophagy induction, and the relevant molecular mechanisms. Results showed that Col2a1, Acan, ghrelin, and autophagy-related markers expression were downregulated, while matrix metalloproteinase 13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) expressions increased in both IL-1β-induced rat chondrocytes and cartilage tissues of OA rats. A total of 130 circRNAs and 731 mRNAs were differentially expressed in IL-1β-induced rat chondrocytes. Among them, we found that circPan3 expression was significantly decreased in both cellular and animal OA models. CircPan3 directly targeted miR-667-5p. CircPan3 overexpression promoted Col2a1, Acan, ghrelin, beclin 1, and LC3-II expression but reduced MMP13 and ADAMTS5 expression in rat chondrocytes, whereas overexpression of miR-667-5p exhibited opposite effects on the above markers. Furthermore, we found that miR-667-5p bound directly to the 3′-UTR sequence of ghrelin gene. Moreover, the circPan3-induced alterations in chondrocytes were antagonized by miR-667-5p overexpression. Taken together, our findings demonstrate that circPan3 promotes ghrelin synthesis and chondrocyte autophagy via targeting miR-667-5p, protecting against OA injury. This study provided experimental evidence that circPan3/miR-667-5p/ghrelin axis might serve as targets of drug development for the treatment of OA.Jing ZengJing ZengZhenzhen ZhangZhenzhen ZhangQing LiaoQijin LuJiemei LiuLixia YuanGang LiuGang LiuFrontiers Media S.A.articlecircPAN3miR-667-5pghrelinchondrocyte autophagyosteoarthritisBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	circPAN3 miR-667-5p ghrelin chondrocyte autophagy osteoarthritis Biology (General) QH301-705.5
spellingShingle	circPAN3 miR-667-5p ghrelin chondrocyte autophagy osteoarthritis Biology (General) QH301-705.5 Jing Zeng Jing Zeng Zhenzhen Zhang Zhenzhen Zhang Qing Liao Qijin Lu Jiemei Liu Lixia Yuan Gang Liu Gang Liu CircPan3 Promotes the Ghrelin System and Chondrocyte Autophagy by Sponging miR-667-5p During Rat Osteoarthritis Pathogenesis
description	This study aimed to investigate the potential roles of circRNAs in regulating osteoarthritis (OA)-related ghrelin synthesis, autophagy induction, and the relevant molecular mechanisms. Results showed that Col2a1, Acan, ghrelin, and autophagy-related markers expression were downregulated, while matrix metalloproteinase 13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) expressions increased in both IL-1β-induced rat chondrocytes and cartilage tissues of OA rats. A total of 130 circRNAs and 731 mRNAs were differentially expressed in IL-1β-induced rat chondrocytes. Among them, we found that circPan3 expression was significantly decreased in both cellular and animal OA models. CircPan3 directly targeted miR-667-5p. CircPan3 overexpression promoted Col2a1, Acan, ghrelin, beclin 1, and LC3-II expression but reduced MMP13 and ADAMTS5 expression in rat chondrocytes, whereas overexpression of miR-667-5p exhibited opposite effects on the above markers. Furthermore, we found that miR-667-5p bound directly to the 3′-UTR sequence of ghrelin gene. Moreover, the circPan3-induced alterations in chondrocytes were antagonized by miR-667-5p overexpression. Taken together, our findings demonstrate that circPan3 promotes ghrelin synthesis and chondrocyte autophagy via targeting miR-667-5p, protecting against OA injury. This study provided experimental evidence that circPan3/miR-667-5p/ghrelin axis might serve as targets of drug development for the treatment of OA.
format	article
author	Jing Zeng Jing Zeng Zhenzhen Zhang Zhenzhen Zhang Qing Liao Qijin Lu Jiemei Liu Lixia Yuan Gang Liu Gang Liu
author_facet	Jing Zeng Jing Zeng Zhenzhen Zhang Zhenzhen Zhang Qing Liao Qijin Lu Jiemei Liu Lixia Yuan Gang Liu Gang Liu
author_sort	Jing Zeng
title	CircPan3 Promotes the Ghrelin System and Chondrocyte Autophagy by Sponging miR-667-5p During Rat Osteoarthritis Pathogenesis
title_short	CircPan3 Promotes the Ghrelin System and Chondrocyte Autophagy by Sponging miR-667-5p During Rat Osteoarthritis Pathogenesis
title_full	CircPan3 Promotes the Ghrelin System and Chondrocyte Autophagy by Sponging miR-667-5p During Rat Osteoarthritis Pathogenesis
title_fullStr	CircPan3 Promotes the Ghrelin System and Chondrocyte Autophagy by Sponging miR-667-5p During Rat Osteoarthritis Pathogenesis
title_full_unstemmed	CircPan3 Promotes the Ghrelin System and Chondrocyte Autophagy by Sponging miR-667-5p During Rat Osteoarthritis Pathogenesis
title_sort	circpan3 promotes the ghrelin system and chondrocyte autophagy by sponging mir-667-5p during rat osteoarthritis pathogenesis
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/74de9082050549e39b83a4c679af6448
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CircPan3 Promotes the Ghrelin System and Chondrocyte Autophagy by Sponging miR-667-5p During Rat Osteoarthritis Pathogenesis

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