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MiRNA-140 is a negative feedback regulator of MMP-13 in IL-1β-stimulated human articular chondrocyte C28/I2 cells

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Abstract

Objective

Osteoarthritis is a degenerative joint disease, in which matrix metalloproteinase (MMP)-13 plays an important role. This study aimed to investigate miRNA-140-mediated negative regulation of MMP-13 expression in interleukin-1β (IL-1β)-stimulated human cartilage cells.

Methods

The human cartilage cell line C28/I2 was cultured in the presence of IL-1β to mimic an osteoarthritic environment. Expression of miRNA-140 and MMP-13 was analyzed after 48 h by real-time RT-PCR and western blot analyses. MiRNA-140 mediated regulation of MMP-13 expression was analyzed by luciferase reporter assays and anti-miRNA-140 oligonucleotide transfection. Furthermore, miRNA-140 and MMP-13 expression was analyzed following DHMEQ treatment.

Results

Expression of miRNA-140 and MMP-13 was elevated in IL-1β-stimulated C28/I2 cells. Bioinformatic prediction showed that the 3′-UTR of MMP-13 mRNA contained a potential binding miRNA-140 site and luciferase mRNA fused with 3′-UTR of MMP-13 mRNA was shown to be repressed by miRNA-140 in reporter assays. Expression of MMP-13 was elevated in IL-1β-stimulated C28/I2 cells following anti-miRNA-140 oligonucleotide transfection. NF-κB activity was inhibited in DHMEQ treated IL-1β-stimulated C28/I2 cells and was associated with decreased miRNA-140 and MMP-13 expression.

Conclusion

Expression of miRNA-140 and MMP-13 was induced by IL-1β. Expression of miRNA-140 inhibited MMP-13 in C28/I2 cells. Expression of miRNA-140 and MMP-13 was shown to be NF-κB-dependent.

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Acknowledgments

This work was supported by grants from the Natural Science Foundation of Guangdong Provence, China (7004817), and the Science and Technology Planning Project of Guangdong Province, China (2007B031400004).

Conflict of interest

The authors state no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Orthopaedics, The 3rd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510240, China

    Zu-jian Liang, Zhao Li & Bai-dang Zhang

  2. Department of Orthopaedics, The 1st Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 12, Jichang Road, Guangzhou, 510405, China

    Hong Zhuang

  3. Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi’an, 710032, China

    Guo-xia Wang

  4. Institute of Orthopaedic Diseases, Jinan University, Guangzhou, 510630, China

    Huan-tian Zhang

  5. Department of Orthopaedics, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China

    Huan-tian Zhang

  6. Department of Hematology, The 3rd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510240, China

    Tian-qi Yu

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  1. Zu-jian Liang
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  2. Hong Zhuang
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  4. Zhao Li
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  5. Huan-tian Zhang
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  7. Bai-dang Zhang
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Correspondence to Hong Zhuang.

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Responsible editor: John Di Battista.

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Liang, Zj., Zhuang, H., Wang, Gx. et al. MiRNA-140 is a negative feedback regulator of MMP-13 in IL-1β-stimulated human articular chondrocyte C28/I2 cells. Inflamm. Res. 61, 503–509 (2012). https://doi.org/10.1007/s00011-012-0438-6

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  • DOI: https://doi.org/10.1007/s00011-012-0438-6

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