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NF-ĸβ upregulates ADAMTS5 expression by direct binding after TNF-α treatment in OUMS-27 chondrosarcoma cell line

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Abstract

Inflammation caused-aggrecan degradation is a critical event in the pathogenesis of osteoarthritis (OA). The aggrecanases like a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) are assumed to be key players in the aggrecan destruction. To develop the comprehensive therapy method for OA, it is essential to elucidate the activation mechanism of ADAMTS5 gene after stimulation of inflammatory cytokines like tumor necrosis factor-α (TNF-α). The cell lines of human chondrosarcoma (OUMS-27) and embryonic kidney (HEK293T) were incubated with tumor necrosis factor-α (TNF-α) for certain time periods, and the expression level of ADAMTS5 was measured in both mRNA and protein levels. Tissue-specific ADAMTS5 activation was founded to be induced after TNF-α treatment. Then, the constructs for the promoter region of ADAMTS5 were prepared and luciferase assay was conducted to understand the involvement mechanism of nuclear factor-kappa beta (NF-ĸβ) in ADAMTS5 activation. It was demonstrated that NF-ĸβ induces the ADAMTS5 expression level by directly binding the promoter region of ADAMTS5. Although the TNF-α blocker is used for OA treatment, the development of a more comprehensive treatment strategy is an urgent need. Our experimental data contributes in terms of selecting NF-ĸβ as a target molecule. Up to date, NF-ĸβ has been proven to involve in the ADAMTS5 up-regulation after several pro-inflammatory cytokines stimulation. In conclusion, our findings make important contributions to the knowledge about the roles of NF-ĸβ in ADAMTS5 activation under inflammatory conditions. So, NF-ĸβ could be considered to be a potential target for OA treatment.

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Acknowledgements

We thank The Scientific and Technological Research Council of Turkey (TUBITAK) for funding the project entitled “The biological Role and Biomarker Potential of ADAMTS Aggrecanases in Chondrocytes” (112S611).

Funding

The scientific And Technological Research Council of Turkey Grant Number: 112611.

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Authors and Affiliations

  1. Department of Medical Genetics, Manisa Celal Bayar University Medical Faculty, Manisa, Turkey

    Dilek Gun Bilgic

  2. Department of Pharmacology, Faculty of Medicine, Kindai University, Osaka, Japan

    Omer Faruk Hatipoglu

  3. Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan

    Sadık Cigdem

  4. Department of Orthopedics and Traumatology, Manisa City Hospital, Manisa, Turkey

    Abdulkadir Bilgic

  5. Department of Medical Genetics, Selcuk University Medical Faculty, Konya, Turkey

    Tulin Cora

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  1. Dilek Gun Bilgic
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  2. Omer Faruk Hatipoglu
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Contributions

Laboratory experiments: DGB, SC, AB, Manuscript preparation: DGB, AB, Study design: OFH, Supervision of laboratory experiments and manuscript preparation: OFH, SC, TC, Data analysis: SC, OFH, DGB All authors read and approved the manuscript.

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Correspondence to Dilek Gun Bilgic.

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Gun Bilgic, D., Hatipoglu, O.F., Cigdem, S. et al. NF-ĸβ upregulates ADAMTS5 expression by direct binding after TNF-α treatment in OUMS-27 chondrosarcoma cell line. Mol Biol Rep 47, 4215–4223 (2020). https://doi.org/10.1007/s11033-020-05514-3

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