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Methotrexate affects HMGB1 expression in rheumatoid arthritis, and the downregulation of HMGB1 prevents rheumatoid arthritis progression

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Abstract

High-mobility group box 1 (HMGB1) is associated with the development of rheumatoid arthritis (RA). Recent studies have shown that methotrexate (MTX) may inhibit the expression of HMGB1. This study examined whether HMGB1 might be involved in the treatment of RA using MTX. Synovial tissues were collected from RA patients who were treated with MTX for at least 6 months (RA-MTX group, 7 cases) and from those without MTX treatment (RA-noMTX group, 7 cases). Additionally, patients with osteoarthritis (OA group, 7 cases) were used as controls. The expression and locations of HMGB1 in the tissues were detected using real-time PCR, western blot, and immunohistochemistry. Additionally, OA-fibroblast-like synoviocytes (FLSs) and RA-FLSs were isolated and cultured, and the expression of HMGB1 was reduced in these cells by transfection with HMGB1 siRNA. Cell proliferation, migration, and invasion abilities were detected. Furthermore, the effects of HMGB1 on matrix metalloproteinase (MMP)-2 and MMP-13 were measured using western blot analysis. At the tissue level, HMGB1 expression in synovial membrane did not differ significantly between the OA and RA-MTX groups, but was significantly lower in these groups than in the RA-noMTX group. In cell experiments, the cell doubling time in the RA-FLS HMGB1 siRNA group was significantly extended compared with that in the RA-FLS negative control (NC)-siRNA group. The amount of cell migration and invasion in the RA-FLS HMGB1 siRNA group was significantly lower compared with that in the NC-siRNA group; the MMP-2 and MMP-13 expression levels were also lower. These results showed that MTX reduced HMGB1 expression in RA synovial tissues, and through the downregulation of HMGB1 expression in tissues, MTX may slow disease progression of RA.

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Acknowledgments

The authors are grateful for the technical advice and the collection of specimens provided by Xi Lan. This work was supported by the National Natural Science Foundations of China (Nos. 81271948 and 81171742).

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Authors and Affiliations

  1. Department of Joint Surgery, Xi’an Hong Hui Hospital, Xi’an Jiaotong University Health Science Center, Xi’an, 710054, Shaanxi Province, China

    Yuan-bo Li, Peng Xu, Ke Xu, Yong-Song Cai & Le Yang

  2. Department of Genetics and Molecular Biology, Xi’an Jiaotong University Health Science Center, Xi’an, 710061, Shaanxi Province, China

    Meng-yao Sun, Jian Sun & She-min Lu

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  1. Yuan-bo Li
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  2. Peng Xu
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  3. Ke Xu
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Correspondence to Peng Xu.

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Li, Yb., Xu, P., Xu, K. et al. Methotrexate affects HMGB1 expression in rheumatoid arthritis, and the downregulation of HMGB1 prevents rheumatoid arthritis progression. Mol Cell Biochem 420, 161–170 (2016). https://doi.org/10.1007/s11010-016-2783-1

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  • DOI: https://doi.org/10.1007/s11010-016-2783-1

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