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Mol Cell Biochem. 2016 Sep;420(1-2):161-70. doi: 10.1007/s11010-016-2783-1. Epub 2016 Aug 13.

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

Author information

1
Department of Joint Surgery, Xi'an Hong Hui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, 710054, Shaanxi Province, China.
2
Department of Joint Surgery, Xi'an Hong Hui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, 710054, Shaanxi Province, China. sousou369@163.com.
3
Department of Genetics and Molecular Biology, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi Province, China.

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.

KEYWORDS:

Fibroblast-like synovial; High-mobility group box 1; Methotrexate; Rheumatoid arthritis

PMID:
27522665
DOI:
10.1007/s11010-016-2783-1
[Indexed for MEDLINE]

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