lncRNA ZFAS1 promotes intervertebral disc degeneration by upregulating AAK1
We investigated the function of lncRNA zinc finger antisense 1 (ZFAS1) in intervertebral disc degeneration (IDD) progression in vitro and in vivo. Nucleus pulposus (NP) tissues were obtained from 20 patients with IDD. IL-1β was used to stimulate primary NP cells to establish the IDD models in vitro....
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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De Gruyter
2022-12-01
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| Series: | Open Medicine |
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| Online Access: | https://doi.org/10.1515/med-2022-0530 |
| _version_ | 1797947737870696448 |
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| author | Wang Zheng Liu Bin Ma Xiangyu Wang Yu Han Wenfeng Xiang Liangbi |
| author_facet | Wang Zheng Liu Bin Ma Xiangyu Wang Yu Han Wenfeng Xiang Liangbi |
| author_sort | Wang Zheng |
| collection | DOAJ |
| description | We investigated the function of lncRNA zinc finger antisense 1 (ZFAS1) in intervertebral disc degeneration (IDD) progression in vitro and in vivo. Nucleus pulposus (NP) tissues were obtained from 20 patients with IDD. IL-1β was used to stimulate primary NP cells to establish the IDD models in vitro. Gene expression was determined by RT-qPCR. 5-Ethynyl-2′-deoxyuridine and flow cytometry were performed to determine cell proliferation and apoptosis, and western blotting was conducted to measure the apoptosis- and extracellular matrix (ECM)-related protein expression. Luciferase reporter assay was used to examine the interactions between the genes. We also investigated the effect of ZFAS1 in a mouse model of IDD induced by needle punctures. Our results showed that ZFAS1 expression was elevated in degenerative NP tissues and IL-1β-treated NP cells. ZFAS1 knockdown inhibited NP cell apoptosis and ECM degradation induced by IL-1β. Mechanically, ZFAS1 sponged miR-4711-5p and adaptor-associated kinase 1 (AAK1) was targeted by miR-4711-5p. Furthermore, AAK1 overexpression partially eliminated the impact of ZFAS1 depletion on NP cell proliferation, apoptosis, and ECM degradation. More importantly, the results of the in vivo studies confirmed the effect of silencing ZFAS1 on alleviating the symptoms of IDD mice. Overall, silencing ZFAS1 inhibits IDD progression by reducing NP cell apoptosis and ECM degradation through the miR-4711-5p/AAK1 axis. |
| first_indexed | 2024-04-10T21:32:28Z |
| format | Article |
| id | doaj.art-3a905d6f2602403f8295e92471c81550 |
| institution | Directory Open Access Journal |
| issn | 2391-5463 |
| language | English |
| last_indexed | 2024-04-10T21:32:28Z |
| publishDate | 2022-12-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Open Medicine |
| spelling | doaj.art-3a905d6f2602403f8295e92471c815502023-01-19T13:04:57ZengDe GruyterOpen Medicine2391-54632022-12-011711973198610.1515/med-2022-0530lncRNA ZFAS1 promotes intervertebral disc degeneration by upregulating AAK1Wang Zheng0Liu Bin1Ma Xiangyu2Wang Yu3Han Wenfeng4Xiang Liangbi5Department of Orthopedics, General Hospital of Northern Theater Command, Shenyang 110016, Liaoning, ChinaDepartment of Orthopedics, General Hospital of Northern Theater Command, Shenyang 110016, Liaoning, ChinaDepartment of Orthopedics, General Hospital of Northern Theater Command, Shenyang 110016, Liaoning, ChinaDepartment of Orthopedics, General Hospital of Northern Theater Command, Shenyang 110016, Liaoning, ChinaDepartment of Orthopedics, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, Liaoning, ChinaDepartment of Orthopedics, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, Liaoning, ChinaWe investigated the function of lncRNA zinc finger antisense 1 (ZFAS1) in intervertebral disc degeneration (IDD) progression in vitro and in vivo. Nucleus pulposus (NP) tissues were obtained from 20 patients with IDD. IL-1β was used to stimulate primary NP cells to establish the IDD models in vitro. Gene expression was determined by RT-qPCR. 5-Ethynyl-2′-deoxyuridine and flow cytometry were performed to determine cell proliferation and apoptosis, and western blotting was conducted to measure the apoptosis- and extracellular matrix (ECM)-related protein expression. Luciferase reporter assay was used to examine the interactions between the genes. We also investigated the effect of ZFAS1 in a mouse model of IDD induced by needle punctures. Our results showed that ZFAS1 expression was elevated in degenerative NP tissues and IL-1β-treated NP cells. ZFAS1 knockdown inhibited NP cell apoptosis and ECM degradation induced by IL-1β. Mechanically, ZFAS1 sponged miR-4711-5p and adaptor-associated kinase 1 (AAK1) was targeted by miR-4711-5p. Furthermore, AAK1 overexpression partially eliminated the impact of ZFAS1 depletion on NP cell proliferation, apoptosis, and ECM degradation. More importantly, the results of the in vivo studies confirmed the effect of silencing ZFAS1 on alleviating the symptoms of IDD mice. Overall, silencing ZFAS1 inhibits IDD progression by reducing NP cell apoptosis and ECM degradation through the miR-4711-5p/AAK1 axis.https://doi.org/10.1515/med-2022-0530intervertebral disc degenerationzfas1apoptosis, ecm degradationaak1 |
| spellingShingle | Wang Zheng Liu Bin Ma Xiangyu Wang Yu Han Wenfeng Xiang Liangbi lncRNA ZFAS1 promotes intervertebral disc degeneration by upregulating AAK1 Open Medicine intervertebral disc degeneration zfas1 apoptosis, ecm degradation aak1 |
| title | lncRNA ZFAS1 promotes intervertebral disc degeneration by upregulating AAK1 |
| title_full | lncRNA ZFAS1 promotes intervertebral disc degeneration by upregulating AAK1 |
| title_fullStr | lncRNA ZFAS1 promotes intervertebral disc degeneration by upregulating AAK1 |
| title_full_unstemmed | lncRNA ZFAS1 promotes intervertebral disc degeneration by upregulating AAK1 |
| title_short | lncRNA ZFAS1 promotes intervertebral disc degeneration by upregulating AAK1 |
| title_sort | lncrna zfas1 promotes intervertebral disc degeneration by upregulating aak1 |
| topic | intervertebral disc degeneration zfas1 apoptosis, ecm degradation aak1 |
| url | https://doi.org/10.1515/med-2022-0530 |
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