ALKBH5-mediated m6A demethylation of HS3ST3B1-IT1 prevents osteoarthritis progression
Summary: HS3ST3B1-IT1 was identified as a downregulated long noncoding RNA in osteoarthritic cartilage. However, its roles and mechanisms in the pathogenesis of osteoarthritis (OA) are unclear. In this study, we demonstrated that the expressions of HS3ST3B1-IT1 and its maternal gene HS3ST3B1 were do...
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| Language: | English |
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Elsevier
2023-10-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223019156 |
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| author | Yuting Tang Yang Liu Xiaoshu Zhu Yanlin Chen Xinluan Jiang Siyang Ding Que Zheng Ming Zhang Jiashu Yang Yunfei Ma Mengying Xing Zongyu Zhang Huimin Ding Yucui Jin Changyan Ma |
| author_facet | Yuting Tang Yang Liu Xiaoshu Zhu Yanlin Chen Xinluan Jiang Siyang Ding Que Zheng Ming Zhang Jiashu Yang Yunfei Ma Mengying Xing Zongyu Zhang Huimin Ding Yucui Jin Changyan Ma |
| author_sort | Yuting Tang |
| collection | DOAJ |
| description | Summary: HS3ST3B1-IT1 was identified as a downregulated long noncoding RNA in osteoarthritic cartilage. However, its roles and mechanisms in the pathogenesis of osteoarthritis (OA) are unclear. In this study, we demonstrated that the expressions of HS3ST3B1-IT1 and its maternal gene HS3ST3B1 were downregulated and positively correlated in osteoarthritic cartilage. Overexpression of HS3ST3B1-IT1 significantly increased chondrocyte viability, inhibited chondrocyte apoptosis, and upregulated extracellular matrix (ECM) proteins, whereas HS3ST3B1-IT1 knockdown had the opposite effects. In addition, HS3ST3B1-IT1 significantly ameliorated monosodium-iodoacetate-induced OA in vivo. Mechanistically, HS3ST3B1-IT1 upregulated HS3ST3B1 expression by blocking its ubiquitination-mediated degradation. Knockdown of HS3ST3B1 reversed the effects of HS3ST3B1-IT1 on chondrocyte viability, apoptosis, and ECM metabolism. AlkB homolog 5 (ALKBH5)-mediated N6-methyladenosine (m6A) demethylation stabilized HS3ST3B1-IT1 RNA. Together, our data revealed that ALKBH5-mediated upregulation of HS3ST3B1-IT1 suppressed OA progression by elevating HS3ST3B1 expression, suggesting that HS3ST3B1-IT1/HS3ST3B1 may serve as potential therapeutic targets for OA treatment. |
| first_indexed | 2024-03-11T15:23:14Z |
| format | Article |
| id | doaj.art-86dc1c82272f45d398d3b916221087ed |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-11T15:23:14Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-86dc1c82272f45d398d3b916221087ed2023-10-28T05:08:42ZengElsevieriScience2589-00422023-10-012610107838ALKBH5-mediated m6A demethylation of HS3ST3B1-IT1 prevents osteoarthritis progressionYuting Tang0Yang Liu1Xiaoshu Zhu2Yanlin Chen3Xinluan Jiang4Siyang Ding5Que Zheng6Ming Zhang7Jiashu Yang8Yunfei Ma9Mengying Xing10Zongyu Zhang11Huimin Ding12Yucui Jin13Changyan Ma14Department of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, P.R. China; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Longmian Road 101, Nanjing, P.R. ChinaDepartment of Orthopedics, Nanjing First Hospital, Nanjing, P.R. ChinaDepartment of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, P.R. ChinaDepartment of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, P.R. ChinaDepartment of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, P.R. ChinaDepartment of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, P.R. ChinaDepartment of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, P.R. ChinaDepartment of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, P.R. ChinaDepartment of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, P.R. ChinaDepartment of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, P.R. ChinaDepartment of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, P.R. ChinaDepartment of Orthopedics, the Traditional Chinese Medical Hospital of Lianyungang, Lianyungang, P.R. China; Corresponding authorDepartment of Orthopedics, BenQ Medical Center, the Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, P.R. China; Corresponding authorDepartment of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, P.R. China; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Longmian Road 101, Nanjing, P.R. China; Corresponding authorDepartment of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, P.R. China; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Longmian Road 101, Nanjing, P.R. China; Corresponding authorSummary: HS3ST3B1-IT1 was identified as a downregulated long noncoding RNA in osteoarthritic cartilage. However, its roles and mechanisms in the pathogenesis of osteoarthritis (OA) are unclear. In this study, we demonstrated that the expressions of HS3ST3B1-IT1 and its maternal gene HS3ST3B1 were downregulated and positively correlated in osteoarthritic cartilage. Overexpression of HS3ST3B1-IT1 significantly increased chondrocyte viability, inhibited chondrocyte apoptosis, and upregulated extracellular matrix (ECM) proteins, whereas HS3ST3B1-IT1 knockdown had the opposite effects. In addition, HS3ST3B1-IT1 significantly ameliorated monosodium-iodoacetate-induced OA in vivo. Mechanistically, HS3ST3B1-IT1 upregulated HS3ST3B1 expression by blocking its ubiquitination-mediated degradation. Knockdown of HS3ST3B1 reversed the effects of HS3ST3B1-IT1 on chondrocyte viability, apoptosis, and ECM metabolism. AlkB homolog 5 (ALKBH5)-mediated N6-methyladenosine (m6A) demethylation stabilized HS3ST3B1-IT1 RNA. Together, our data revealed that ALKBH5-mediated upregulation of HS3ST3B1-IT1 suppressed OA progression by elevating HS3ST3B1 expression, suggesting that HS3ST3B1-IT1/HS3ST3B1 may serve as potential therapeutic targets for OA treatment.http://www.sciencedirect.com/science/article/pii/S2589004223019156OrthopedicsBiological sciencesMolecular biologyMolecular mechanism of gene regulation |
| spellingShingle | Yuting Tang Yang Liu Xiaoshu Zhu Yanlin Chen Xinluan Jiang Siyang Ding Que Zheng Ming Zhang Jiashu Yang Yunfei Ma Mengying Xing Zongyu Zhang Huimin Ding Yucui Jin Changyan Ma ALKBH5-mediated m6A demethylation of HS3ST3B1-IT1 prevents osteoarthritis progression iScience Orthopedics Biological sciences Molecular biology Molecular mechanism of gene regulation |
| title | ALKBH5-mediated m6A demethylation of HS3ST3B1-IT1 prevents osteoarthritis progression |
| title_full | ALKBH5-mediated m6A demethylation of HS3ST3B1-IT1 prevents osteoarthritis progression |
| title_fullStr | ALKBH5-mediated m6A demethylation of HS3ST3B1-IT1 prevents osteoarthritis progression |
| title_full_unstemmed | ALKBH5-mediated m6A demethylation of HS3ST3B1-IT1 prevents osteoarthritis progression |
| title_short | ALKBH5-mediated m6A demethylation of HS3ST3B1-IT1 prevents osteoarthritis progression |
| title_sort | alkbh5 mediated m6a demethylation of hs3st3b1 it1 prevents osteoarthritis progression |
| topic | Orthopedics Biological sciences Molecular biology Molecular mechanism of gene regulation |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223019156 |
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