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MicroRNA-199-3p up-regulation enhances chondrocyte proliferation and inhibits apoptosis in knee osteoarthritis via DNMT3A repression

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Abstract

Aim

Studies have pivoted on the position of microRNAs (miRNAs) in knee osteoarthritis (KOA) but not the more specific function of miR-199-3p. Thus, this study is to uncover the mechanism of miR-199-3p in KOA.

Methods

Rats KOA models were established by modified Hulth method. miR-199-3p expression was observed in cartilage of KOA rats. The binding sites of miR-199-3p were predicted by bioinformatics analysis and the potential interaction between DNA methyltransferase 3A (DNMT3A) and miR-199-3p was verified by dual-luciferase reporter gene assay. Rats were injected with miR-199-3p agomir or antagomir and DNMT3A siRNA into the knee joint. Inflammatory response factors in serum and cartilage tissues, cell apoptosis, and pathological status of cartilage tissues were detected. Chondrocytes were isolated from KOA cartilages and treated with miR-199-3p mimic or inhibitor and DNMT3A siRNA. Chondrocyte proliferation and apoptosis were detected.

Results

miR-199-3p expression was suppressed in cartilage of KOA rats. Dual-luciferase reporter gene assay proved that a miR-199-3p-binding site was located in the 3′UTR of DNMT3A mRNA. Inflammation, chondrocyte apoptosis and cartilage pathological changes were improved by miR-199-3p agomir but aggravated by miR-199-3p antagomir. The effects of miR-199-3p antagomir on KOA rats were partially reversed by DNMT3A siRNA. miR-199-3p mimic or DNMT3A siRNA decreased KOA chondrocytes apoptosis and promoted proliferation. miR-199-3p inhibitor showed the opposite functions to miR-199-3p mimic. The effects of miR-199-3p inhibitor on chondrocytes were reversed by DNMT3A siRNA.

Conclusion

This study highlights that miR-199-3p up-regulation or down-regulation of DNMT3A induces chondrocyte proliferation and inhibits apoptosis in KOA, which may widen our eyes to treat patients with KOA.

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Acknowledgements

We would like to acknowledge the reviewers for their helpful comments on this paper.

Funding

This work was supported by Jiangsu Provincial Commission of Health and Family Planning (H201619).

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Author notes

  1. Wenqi Gu and Zhongmin Shi are Co-first authors.

Authors and Affiliations

  1. Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu Province, People’s Republic of China

    Wenqi Gu & Hongtao Zhang

  2. Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, People’s Republic of China

    Wenqi Gu, Zhongmin Shi & Guoxun Song

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  1. Wenqi Gu
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  2. Zhongmin Shi
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  3. Guoxun Song
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  4. Hongtao Zhang
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Correspondence to Hongtao Zhang.

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Gu, W., Shi, Z., Song, G. et al. MicroRNA-199-3p up-regulation enhances chondrocyte proliferation and inhibits apoptosis in knee osteoarthritis via DNMT3A repression. Inflamm. Res. 70, 171–182 (2021). https://doi.org/10.1007/s00011-020-01430-1

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