Down-regulated ciRS-7/up-regulated miR-7 axis aggravated cartilage degradation and autophagy defection by PI3K/AKT/mTOR activation mediated by IL-17A in osteoarthritis
Osteoarthritis (OA) is one of the most painful and widespread chronic degenerative joint diseases and is characterized by destructed articular cartilage and inflamed joints. Previously, our findings indicated that circular RNA ciRS-7 (ciRS-7)/microRNA 7 (miR-7) axis is abnormally expressed in OA, and regulates proliferation, inflammatory responses, and apoptosis of interleukin-1β (IL-1β)-stimulated chondrocytes. However, its underlying role in OA remains unknown. In this study, we first validated cartilage degradation and defection of autophagy in samples of OA patients. IL-1β initially stimulated autophagy of chondrocytes, and ultimately significantly suppressed autophagy. Upregulated ciRS-7/down-regulated miR-7 aggravated IL-1β-induced cartilage degradation, and restrained autophagy in vitro. Gene sequencing and bioinformatics analysis performed on a control group, IL-1β group, and IL-1β+miR-7-mimics group demonstrated that seven of the most significant mRNA candidates were enriched in the interleukin-17 (IL-17) signaling pathway. Increased IL-17A levels were also observed by qRT-PCR and ELISA. In addition, it was revealed that the ciRS-7/miR-7 axis ameliorated cartilage degradation and defection of autophagy by PI3K/AKT/mTOR activation in IL-1β-induced chondrocytes. Furthermore, an OA model was established in rats with medial meniscus destabilization. miR-7-siRNA-expressing lentiviruses alleviated surgical resection-induced cartilage destruction of OA mice, whereas miR-7 mimics worsened the effects. Thus, these findings revealed that the mechanism of the ciRS-7/miR-7 axis involved regulating OA progression and provided valuable directions for OA treatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Aging - 12(2020), 20 vom: 25. Okt., Seite 20163-20183 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhou, Xindie [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 19.04.2021 Date Revised 04.12.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.18632/aging.103731 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM316683663 |
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| 100 | 1 | |a Zhou, Xindie |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Down-regulated ciRS-7/up-regulated miR-7 axis aggravated cartilage degradation and autophagy defection by PI3K/AKT/mTOR activation mediated by IL-17A in osteoarthritis |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 19.04.2021 | ||
| 500 | |a Date Revised 04.12.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Osteoarthritis (OA) is one of the most painful and widespread chronic degenerative joint diseases and is characterized by destructed articular cartilage and inflamed joints. Previously, our findings indicated that circular RNA ciRS-7 (ciRS-7)/microRNA 7 (miR-7) axis is abnormally expressed in OA, and regulates proliferation, inflammatory responses, and apoptosis of interleukin-1β (IL-1β)-stimulated chondrocytes. However, its underlying role in OA remains unknown. In this study, we first validated cartilage degradation and defection of autophagy in samples of OA patients. IL-1β initially stimulated autophagy of chondrocytes, and ultimately significantly suppressed autophagy. Upregulated ciRS-7/down-regulated miR-7 aggravated IL-1β-induced cartilage degradation, and restrained autophagy in vitro. Gene sequencing and bioinformatics analysis performed on a control group, IL-1β group, and IL-1β+miR-7-mimics group demonstrated that seven of the most significant mRNA candidates were enriched in the interleukin-17 (IL-17) signaling pathway. Increased IL-17A levels were also observed by qRT-PCR and ELISA. In addition, it was revealed that the ciRS-7/miR-7 axis ameliorated cartilage degradation and defection of autophagy by PI3K/AKT/mTOR activation in IL-1β-induced chondrocytes. Furthermore, an OA model was established in rats with medial meniscus destabilization. miR-7-siRNA-expressing lentiviruses alleviated surgical resection-induced cartilage destruction of OA mice, whereas miR-7 mimics worsened the effects. Thus, these findings revealed that the mechanism of the ciRS-7/miR-7 axis involved regulating OA progression and provided valuable directions for OA treatment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a IL-17A | |
| 650 | 4 | |a autophagy | |
| 650 | 4 | |a ciRS-7 | |
| 650 | 4 | |a miR-7 | |
| 650 | 4 | |a osteoarthritis | |
| 650 | 7 | |a IL17A protein, human |2 NLM | |
| 650 | 7 | |a Interleukin-17 |2 NLM | |
| 650 | 7 | |a Interleukin-1beta |2 NLM | |
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| 650 | 7 | |a EC 2.7.1.1 |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins c-akt |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a TOR Serine-Threonine Kinases |2 NLM | |
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| 700 | 1 | |a Li, Jin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Yuanshuai |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Zhicheng |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Haoyu |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Dong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Junjie |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Nanwei |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Yong |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Lifeng |e verfasserin |4 aut | |
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