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Circ_0136474 promotes the progression of osteoarthritis by sponging mir-140-3p and upregulating MECP2

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Abstract

Background: Circular RNAs (circRNAs) have pivotal roles in the progression of many diseases, including osteoarthritis (OA). The detained function and regulatory mechanism of circ_0136474 in OA are still largely unknown. Methods: The chondrocytes (CHON-001 cells) were exposed to interleukin-1 beta (IL-1β) to mimic the injury in OA. The expression levels of circ_0136474, microRNA-140-3p (miR-140-3p), methyl-CpG-binding protein 2 (MECP2) mRNA were measured by qRT-PCR. Cell proliferation was assessed using CCK-8 assay. Flow cytometry was employed for measuring cell apoptosis. All protein levels were evaluated via western blot analysis. ELISA was used for detecting the concentrations of the inflammatory cytokines. Dual-luciferase reporter analysis and RNA Immunoprecipitation analysis were conducted for confirming the association between miR-140-3p and circ_0136474 or MECP2. Results: Circ_0136474 was upregulated in IL-1β-induced CHON-001 cells and OA cartilage tissues. Circ_0136474 deficiency alleviated IL-1β-stimulated CHON-001 cell damage via enhancing cell proliferation and reducing extracellular matrix (ECM) degradation, apoptosis, and inflammation. Circ_0136474 was a sponge of miR-140-3p, and miR-140-3p inhibition reversed the roles of circ_0136474 knockdown in IL-1β-treated CHON-001 cells. Moreover, miR-140-3p directly targeted MECP2, and upregulation of miR-140-3p attenuated L-1β-triggered CHON-001 cell injury via targeting MECP2. Additionally, circ_0136474 regulated MECP2 level via sponging miR-140-3p. Conclusion: Circ_0136474 knockdown alleviated IL-1β-triggered CHON-001 cell damage through modulation of miR-140-3p/MECP2 axis, indicating a new target for treatment of OA.

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Acknowledgements

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Funding

This work was supported by National Natural Science Foundation of China (No. 81672154).

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Authors and Affiliations

  1. Department of Orthopedics, Renmin Hospital, Wuhan University, Wuhan City, Hubei Province, China

    Shile Cheng, Zhigang Nie, Jiarui Cao & Hao Peng

  2. Department of Orthopedics, Renmin Hospital, Wuhan University, No. 99 Zhangzhidong Road, Wuchang District, 430060, Wuhan, Hubei Province, China

    Hao Peng

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  1. Shile Cheng
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Shile Cheng conceived the project. Shile Cheng and Zhigang Nie designed and performed experiments. Jiarui Cao analyzed and interpreted the data. Hao Peng was responsible for drafting the manuscript. All authors read and approved the final manuscript.

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Correspondence to Hao Peng.

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Cheng, S., Nie, Z., Cao, J. et al. Circ_0136474 promotes the progression of osteoarthritis by sponging mir-140-3p and upregulating MECP2. J Mol Histol 54, 1–12 (2023). https://doi.org/10.1007/s10735-022-10100-x

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  • DOI: https://doi.org/10.1007/s10735-022-10100-x

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