CircSCAPER knockdown attenuates IL-1β-induced chondrocyte injury by miR-127-5p/TLR4 axis in osteoarthritis
Purpose Osteoarthritis (OA) is a chronic inflammatory degenerative disease characterized by articular cartilage degradation. Circular RNAs have been shown to play significant roles in OA process. Herein, this work aimed to investigate the potential role and mechanism of circSCAPER in OA progression....
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-11-01
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| Series: | Autoimmunity |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/08916934.2022.2103798 |
| _version_ | 1797684591663775744 |
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| author | Yuchang Zhang Ping Zhao Sen Li Xiangqian Mu Huaqi Wang |
| author_facet | Yuchang Zhang Ping Zhao Sen Li Xiangqian Mu Huaqi Wang |
| author_sort | Yuchang Zhang |
| collection | DOAJ |
| description | Purpose Osteoarthritis (OA) is a chronic inflammatory degenerative disease characterized by articular cartilage degradation. Circular RNAs have been shown to play significant roles in OA process. Herein, this work aimed to investigate the potential role and mechanism of circSCAPER in OA progression. Methods Levels of circSCAPER, miR-127-5p and toll-like receptor 4 (TLR4) were detected by qRT-PCR or western blotting. Cell apoptosis was determined by flow cytometry. The expression of Aggrecan and Matrix metallopeptidase was examined using western blot to assess extracellular matrix (ECM) degradation. Inflammatory response and oxidative stress were determined by measuring the release of inflammatory factors, along with the generation of intracellular reactive oxygen species and malondialdehyde. The interaction between miR-127-5p and circSCAPER or TLR4 was determined by dual-luciferase reporter, RNA immunoprecipitation and pull-down assays. Results Chondrocytes were treated with interleukin-1β (IL-1β) to mimic OA condition in vitro. CircSCAPER was increased in OA cartilages and IL-1β-induced chondrocytes. Functionally, knockdown of circSCAPER attenuated IL-1β-evoked apoptosis, ECM degradation, inflammation and oxidative stress in vitro. CircSCAPER up-regulation in OA cartilages was discovered to be accompanied by decreased miR-127-5p and increased TLR4. Mechanistically, circSCAPER acted as a sponge for miR-127-5p to positively regulate TLR4 expression in chondrocytes. IL-1β treatment reduced miR-127-5p expression but up-regulated TLR4 expression, re-expression of miR-127-5p suppressed IL-1β-caused chondrocyte injury, which was abolished by TLR4 overexpression. Moreover, miR-127-5p inhibition reversed the protective action of circSCAPER knockdown on chondrocytes under IL-1β treatment. Conclusion CircSCAPER silencing protected against IL-1β-induced apoptosis, ECM degradation, inflammation and oxidative stress in chondrocytes via miR-127-5p/TLR4 axis. |
| first_indexed | 2024-03-12T00:32:00Z |
| format | Article |
| id | doaj.art-2f9db62972b84e9ba2acdd528d033109 |
| institution | Directory Open Access Journal |
| issn | 0891-6934 1607-842X |
| language | English |
| last_indexed | 2024-03-12T00:32:00Z |
| publishDate | 2022-11-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autoimmunity |
| spelling | doaj.art-2f9db62972b84e9ba2acdd528d0331092023-09-15T10:12:25ZengTaylor & Francis GroupAutoimmunity0891-69341607-842X2022-11-0155857758610.1080/08916934.2022.21037982103798CircSCAPER knockdown attenuates IL-1β-induced chondrocyte injury by miR-127-5p/TLR4 axis in osteoarthritisYuchang Zhang0Ping Zhao1Sen Li2Xiangqian Mu3Huaqi Wang4Department of Orthopedics, Gansu Provincial Hospital of Traditional Chinese MedicineDepartment of Orthopedics, Gansu Provincial Hospital of Traditional Chinese MedicineDepartment of Orthopedics, Gansu Provincial Hospital of Traditional Chinese MedicineDepartment of Orthopedics, Gansu Provincial Hospital of Traditional Chinese MedicineDepartment of Orthopedics, Ankang Traditional Chinese Medicine HospitalPurpose Osteoarthritis (OA) is a chronic inflammatory degenerative disease characterized by articular cartilage degradation. Circular RNAs have been shown to play significant roles in OA process. Herein, this work aimed to investigate the potential role and mechanism of circSCAPER in OA progression. Methods Levels of circSCAPER, miR-127-5p and toll-like receptor 4 (TLR4) were detected by qRT-PCR or western blotting. Cell apoptosis was determined by flow cytometry. The expression of Aggrecan and Matrix metallopeptidase was examined using western blot to assess extracellular matrix (ECM) degradation. Inflammatory response and oxidative stress were determined by measuring the release of inflammatory factors, along with the generation of intracellular reactive oxygen species and malondialdehyde. The interaction between miR-127-5p and circSCAPER or TLR4 was determined by dual-luciferase reporter, RNA immunoprecipitation and pull-down assays. Results Chondrocytes were treated with interleukin-1β (IL-1β) to mimic OA condition in vitro. CircSCAPER was increased in OA cartilages and IL-1β-induced chondrocytes. Functionally, knockdown of circSCAPER attenuated IL-1β-evoked apoptosis, ECM degradation, inflammation and oxidative stress in vitro. CircSCAPER up-regulation in OA cartilages was discovered to be accompanied by decreased miR-127-5p and increased TLR4. Mechanistically, circSCAPER acted as a sponge for miR-127-5p to positively regulate TLR4 expression in chondrocytes. IL-1β treatment reduced miR-127-5p expression but up-regulated TLR4 expression, re-expression of miR-127-5p suppressed IL-1β-caused chondrocyte injury, which was abolished by TLR4 overexpression. Moreover, miR-127-5p inhibition reversed the protective action of circSCAPER knockdown on chondrocytes under IL-1β treatment. Conclusion CircSCAPER silencing protected against IL-1β-induced apoptosis, ECM degradation, inflammation and oxidative stress in chondrocytes via miR-127-5p/TLR4 axis.http://dx.doi.org/10.1080/08916934.2022.2103798circscapermir-127-5ptlr4chondrocyteosteoarthritisextracellular matrix |
| spellingShingle | Yuchang Zhang Ping Zhao Sen Li Xiangqian Mu Huaqi Wang CircSCAPER knockdown attenuates IL-1β-induced chondrocyte injury by miR-127-5p/TLR4 axis in osteoarthritis Autoimmunity circscaper mir-127-5p tlr4 chondrocyte osteoarthritis extracellular matrix |
| title | CircSCAPER knockdown attenuates IL-1β-induced chondrocyte injury by miR-127-5p/TLR4 axis in osteoarthritis |
| title_full | CircSCAPER knockdown attenuates IL-1β-induced chondrocyte injury by miR-127-5p/TLR4 axis in osteoarthritis |
| title_fullStr | CircSCAPER knockdown attenuates IL-1β-induced chondrocyte injury by miR-127-5p/TLR4 axis in osteoarthritis |
| title_full_unstemmed | CircSCAPER knockdown attenuates IL-1β-induced chondrocyte injury by miR-127-5p/TLR4 axis in osteoarthritis |
| title_short | CircSCAPER knockdown attenuates IL-1β-induced chondrocyte injury by miR-127-5p/TLR4 axis in osteoarthritis |
| title_sort | circscaper knockdown attenuates il 1β induced chondrocyte injury by mir 127 5p tlr4 axis in osteoarthritis |
| topic | circscaper mir-127-5p tlr4 chondrocyte osteoarthritis extracellular matrix |
| url | http://dx.doi.org/10.1080/08916934.2022.2103798 |
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