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ALKBH5-mediated m6A demethylation of HS3ST3B1-IT1 prevents osteoarthritis progression.
Tang, Yuting; Liu, Yang; Zhu, Xiaoshu; Chen, Yanlin; Jiang, Xinluan; Ding, Siyang; Zheng, Que; Zhang, Ming; Yang, Jiashu; Ma, Yunfei; Xing, Mengying; Zhang, Zongyu; Ding, Huimin; Jin, Yucui; Ma, Changyan.
Afiliação
  • Tang Y; Department of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, P.R. China.
  • Liu Y; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Longmian Road 101, Nanjing, P.R. China.
  • Zhu X; Department of Orthopedics, Nanjing First Hospital, Nanjing, P.R. China.
  • Chen Y; Department of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, P.R. China.
  • Jiang X; Department of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, P.R. China.
  • Ding S; Department of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, P.R. China.
  • Zheng Q; Department of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, P.R. China.
  • Zhang M; Department of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, P.R. China.
  • Yang J; Department of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, P.R. China.
  • Ma Y; Department of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, P.R. China.
  • Xing M; Department of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, P.R. China.
  • Zhang Z; Department of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, P.R. China.
  • Ding H; Department of Orthopedics, the Traditional Chinese Medical Hospital of Lianyungang, Lianyungang, P.R. China.
  • Jin Y; Department of Orthopedics, BenQ Medical Center, the Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, P.R. China.
  • Ma C; Department of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, P.R. China.
iScience ; 26(10): 107838, 2023 Oct 20.
Article em En | MEDLINE | ID: mdl-37752950
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.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article