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Inhibition of microRNA-495 suppresses chondrocyte apoptosis through activation of the NF-κB signaling pathway by regulating CCL4 in osteoarthritis

Gene Therapy volume 26, pages 217–229 (2019)Cite this article

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Abstract

As a common form of arthritis, osteoarthritis (OA) represents a degenerative disease, characterized by articular cartilage damage and synovium inflammation. Recently, the role of various microRNAs (miRs) and their specific expression in OA has been highlighted. Therefore, the aim of the current study was to elucidate the role by which miR-495 and chemokine ligand 4 (CCL4) influence the development and progression of OA. OA mice models were established, after which the CCL4 and collagen levels as well as cell apoptosis were determined in cartilage tissue of OA mice. The chondrocytes of the OA mice models were subsequently treated with a series of miR-495 mimic, inhibitor, and siRNA against CCL4. Afterwards, miR-495 expressions as well as the levels of CCL4, p50, p65, and IkBa and the extent of IkBa phosphorylation in addition to the luciferase activity of NF-kB were measured accordingly. Finally, cell apoptosis and cell cycle distribution were detected. miR-495 was highly expressed while NF-κB, CCL4, and collagen II were poorly expressed. Cell apoptosis was elevated in the cartilage tissue of the OA mice. CCL4 was a potential target gene of miR-495. Downregulation of miR-495 led to accelerated chondrocyte proliferation accompanied by diminished cell apoptosis among the OA mice. Taken together, the results of the current study demonstrated that inhibition of miR-495 suppressed chondrocyte apoptosis and promoted its proliferation through activation of the NF-κB signaling pathway by up-regulation of CCL4 in OA.

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Acknowledgements

This study was supported by Key Project of Harbin Municipal Science and Technology Bureau (No. 2016RAXYJ068).

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Authors and Affiliations

  1. Department of Orthopaedics, The Fourth Affiliated Hospital of Harbin Medical University, 150001, Harbin, China

    Da-Wei Yang, Gui-Bin Qian, Ming-Jiu Jiang & Peng Wang

  2. Department of Orthopaedics, The Second Affiliated Hospital of Xi’an Jiaotong University, 710000, Xi’an, China

    Kun-Zheng Wang

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Yang, DW., Qian, GB., Jiang, MJ. et al. Inhibition of microRNA-495 suppresses chondrocyte apoptosis through activation of the NF-κB signaling pathway by regulating CCL4 in osteoarthritis. Gene Ther 26, 217–229 (2019). https://doi.org/10.1038/s41434-019-0068-5

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