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LncRNA AC005165.1 Alleviates IL-1β-Induced Osteoarthritis via miR-199a-3p/TXNIP Axis

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Abstract

Osteoarthritis (OA) is a chronic musculoskeletal disease and often causes impaired joint mobility and disability. Long noncoding RNAs (lncRNAs) play pivotal roles in OA development. This study was done to explore the role and mechanism of the lncRNA AC005165.1 in the cell model of interleukin-1β (IL)-1β-treated chondrocytes. This study recruited 20 surgically treated OA patients and 12 age- and gender-matched controls. Real-time reverse transcription quantitative polymerase chain reaction was used to examine the expression levels of AC005165.1, miR-199a-3p, and thioredoxin-interacting protein (TXNIP) in articular cartilage of patients and IL-1β-treated human chondrocytes. Cell viability and apoptosis were evaluated by cell counting kit‐8 and flow cytometry assays, respectively. The protein levels of inflammatory cytokines were assessed by western blotting. Enzyme‐linked immunosorbent assay was conducted to detect the concentrations of the inflammatory cytokines in chondrocytes. Luciferase reporter assay and Pearson’s correlation analysis were used for analyzing the interaction and the correlation among AC005165.1, miR-199a-3p, and TXNIP. AC005165.1 expression was downregulated in cartilage of OA patients and chondrocytes treated with IL-1β, compared to that in the control groups. AC005165.1 knockdown increased apoptosis and aggravated inflammatory response in IL-1β-treated chondrocytes. AC005165.1 interacted with miR-199a-3p, and TXNIP was targeted by miR-199a-3p. In rescue assay, miR-199a-3p knockdown and TXNIP overexpression significantly reduced apoptosis and mitigated inflammatory response in IL-1β-treated chondrocytes with AC005165.1 knockdown. AC005165.1 knockdown promoted apoptosis and inflammatory response in IL-1β-treated chondrocytes via the miR-199a-3p/TXNIP axis.

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Data Availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

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Funding

This work was supported by Wuhan Municipal Health Commission (No. WZ15B09).

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Authors and Affiliations

  1. Department of Orthopedics, Wuhan Hospital of Traditional Chinese Medicine, No. 49 Lihuangpi Road, Jiang’an District, Wuhan, 430014, China

    Xi Gu & Tian Xie

Authors
  1. Xi Gu
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  2. Tian Xie
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Contributions

XG were the main designers of this study. XG and TX performed the experiments and analyzed the data. XG and TX drafted the manuscript. All authors read and approved the final manuscript.

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Correspondence to Tian Xie.

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The authors declare that they have no competing interests.

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The study was approved by the Medical Ethics Committee of Wuhan Hospital of Traditional Chinese Medicine and informed consent of all patients was obtained.

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Gu, X., Xie, T. LncRNA AC005165.1 Alleviates IL-1β-Induced Osteoarthritis via miR-199a-3p/TXNIP Axis. Biochem Genet (2024). https://doi.org/10.1007/s10528-024-10720-w

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