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MIR-140-5p affects chondrocyte proliferation, apoptosis, and inflammation by targeting HMGB1 in osteoarthritis

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Abstract

Objective

This study aimed to test the expression and biological function of miR-140-5p in osteoarthritis (OA), and identify its target gene and explore its mechanism in OA.

Methods

Differential genes were screened and analyzed by gene microarray and WGCNA analysis. The normal human chondrocytes C28/I2 were induced by IL-1β to construct the OA cell model. The expression of miR-140-5p and high mobility group box 1 (HMGB1) was quantified by quantitative real-time PCR (qRT-PCR) in OA tissues and IL-1β-induced chondrocytes. Western blotting was performed to evaluate the expression of HMGB1 and PI3K/AKT pathway activation. The concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6, MMP-1 and MMP-3 were determined by ELISA. CCK-8 and flow cytometry were conducted to determine the cellular capabilities of proliferation and cell apoptosis.

Results

Bioinformatics analysis demonstrated that HMGB1 was highly expressed in OA and activated PI3K/AKT pathway. Also, HMGB1 was predicted as a target of miR-140-5p. The levels of miR-140-5p were negatively correlated with HMGB1 in OA tissues and IL-1β-induced chondrocytes. The overexpression of miR-140-5p reduced the expression of HMGB1 protein, p-AKT (Ser473) and p-PI3K in IL-1β-induced chondrocytes. Besides, the expression of p-AKT (Ser473) and p-PI3K was significantly upregulated by employing miR-140-5p inhibitor, but retrieved after treating with LY294002. Furthermore, miR-140-5p inhibited inflammation, matrix metalloprotease expression and apoptosis in IL-1β-induced chondrocytes through regulating HMGB1.

Conclusion

MiR-140-5p was down-regulated while HMGB1 was upregulated in OA. MiR-140-5p could inhibit the PI3K/AKT signaling pathway and suppress the progression of OA through targeting HMGB1.

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Acknowledgements

The study was supported by Natural Science Foundation of China [Grant Numbers: 81630064; 81871786].

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Authors and Affiliations

  1. Department of Orthopedics, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, No.1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China

    Yingjie Wang, Zeng Li, Weifeng Li & Xisheng Weng

  2. Department of Orthopedics, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China

    Songpo Shen

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Correspondence to Xisheng Weng.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of Peking Union Medical College Hospital and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

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Wang, Y., Shen, S., Li, Z. et al. MIR-140-5p affects chondrocyte proliferation, apoptosis, and inflammation by targeting HMGB1 in osteoarthritis. Inflamm. Res. 69, 63–73 (2020). https://doi.org/10.1007/s00011-019-01294-0

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  • DOI: https://doi.org/10.1007/s00011-019-01294-0

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