CircFNDC3B regulates osteoarthritis and oxidative stress by targeting miR-525-5p/HO-1 axis.

CircFNDC3B regulates osteoarthritis and oxidative stress by targeting miR-525-5p/HO-1 axis.
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DOI:
10.1038/s42003-023-04569-9
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发表时间:
2023-02-20
影响因子:
5.9
通讯作者:
--
中科院分区:
生物学2区
文献类型:
--
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骨关节炎是一种常见的慢性退行性关节疾病,与多种危险因素有关,包括衰老、遗传、肥胖和机械障碍。本研究旨在阐明新近发现的环状核糖核酸(CircRNA)CircFNDC3B在骨性关节炎发生发展中的作用及其与NF-κB信号通路和氧化应激的关系。通过荧光原位杂交、实时聚合酶链式反应、免疫印迹、免疫荧光分析、荧光素酶报告分析、下拉实验和活性氧分析,研究了FNDC3B/MIR525-5p/HO-1轴及其与NF-κB信号通路和氧化应激的关系。在体内外研究了CircFNDC3B在骨性关节炎中的作用。这些评估表明,CircFNDC3B促进了软骨细胞的增殖,并保护细胞外基质(ECM)免受降解。我们还揭示了CircFNDC3B通过调节CircFNDC3B/miR-525-5p/HO-1轴和NF-κB信号通路来防御OA的氧化应激。此外,我们发现,过表达CircFNDC3B可以减轻兔模型中的骨性关节炎。综上所述,我们发现了一个新的信号通路FNDC3B/MIR-525-5P/HO-1,该信号通路可能通过减轻氧化应激和调节NF-κB通路而减轻骨性关节炎,从而对软骨细胞的细胞外基质产生保护作用,使其成为治疗骨性关节炎的潜在治疗靶点。FNDC3B周围的环状核糖核酸通过氧化应激和HO-1/NF-κB信号通路调节骨关节炎的进展。
Osteoarthritis (OA) is a common chronic degenerative joint disease associated with a variety of risk factors including aging, genetics, obesity, and mechanical disturbance. This study aimed to elucidate the function of a newly discovered circular RNA (circRNA), circFNDC3B, in OA progression and its relationship with the NF-κB signaling pathway and oxidative stress. The circFNDC3B/miR-525-5p/HO-1 axis and its relationship with the NF-κB signaling pathway and oxidative stress were investigated and validated using fluorescence in situ hybridization, real-time PCR, western blotting, immunofluorescence analysis, luciferase reporter assays, pull-down assays, and reactive oxygen species analyses. The functions of circFNDC3B in OA was investigated in vitro and in vivo. These evaluations demonstrated that circFNDC3B promotes chondrocyte proliferation and protects the extracellular matrix (ECM) from degradation. We also revealed that circFNDC3B defends against oxidative stress in OA by regulating the circFNDC3B/miR-525-5p/HO-1 axis and the NF-κB signaling pathway. Further, we found that overexpression of circFNDC3B alleviated OA in a rabbit model. In summary, we identified a new circFNDC3B/miR-525-5p/HO-1 signaling pathway that may act to relieve OA by alleviating oxidative stress and regulating the NF-κB pathway, resulting in the protection of the ECM in human chondrocytes, highlighting it as a potential therapeutic target for the treatment of OA. Circular RNA circFNDC3B regulates osteoarthritis progression via oxidative stress and HO-1/ NF-κB signalling pathways.
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