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Circ_0045714 alleviates TNF-α-induced chondrocyte injury and extracellular matrix degradation through miR-218-5p/HRAS axis

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Abstract

Emerging evidence suggests that dysregulated circular RNAs (circRNAs) play a pivotal role in osteoarthritis (OA). Circ_0045714 is a functional circRNAs, and has been revealed to involve in the process of OA. However, the molecular mechanisms by which circ_0045714 regulates OA progression are not thoroughly elucidated. Circ_0045714 expression was decreased in OA and TNF-α-induced chondrocytes, ectopic overexpression of circ_0045714 abolished TNF-α-induced cell apoptosis, inflammation, extracellular matrix (ECM) degradation promotion and proliferation inhibition. In a mechanical study, circ_0045714 targeted miR-218-5p, and miR-218-5p overexpression reversed the effects of circ_0045714 on TNF-α-induced chondrocytes. Besides that, HRAS was a target of miR-218-5p, and HRAS knockdown attenuated the protective effects of miR-218-5p inhibition on TNF-α-induced chondrocyte dysfunction. Additionally, circ_0045714 could regulate HRAS expression via miR-218-5p in chondrocytes. Up-regulation of circ_0045714 suppressed TNF-α-induced chondrocyte growth inhibition, inflammation, and ECM degradation via miR-218-5p/HRAS axis, suggesting a novel insight into the pathogenesis of OA and the potential protective role of circ_0045714 in the occurrence and development of OA.

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Authors and Affiliations

  1. Department of Orthopedics, The Affiliated No. 1 People’s Hospital of Nangjing Medical University, No.1, Huanghe West Road, Huaiyin District, Huai’an, 223300, China

    Haitao Jiang, Jian Dai, Cheng Zhang, Hailang Sun & Xiaoming Tang

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  1. Haitao Jiang
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  2. Jian Dai
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  3. Cheng Zhang
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  4. Hailang Sun
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  5. Xiaoming Tang
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Correspondence to Xiaoming Tang.

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Jiang, H., Dai, J., Zhang, C. et al. Circ_0045714 alleviates TNF-α-induced chondrocyte injury and extracellular matrix degradation through miR-218-5p/HRAS axis. J Bioenerg Biomembr 53, 97–107 (2021). https://doi.org/10.1007/s10863-020-09868-y

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  • DOI: https://doi.org/10.1007/s10863-020-09868-y

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