What question did this study set out to answer?

To identify therapeutic gene targets and epigenetic modifications modulated by methotrexate, JAK inhibitors, and (5R)-5-hydroxytriptolide (LLDT-8) in rheumatoid arthritis fibroblast-like synoviocytes.

May 5, 2025Biochemistry and Biophysics ReportsOpen Access

Therapeutic gene targets and epigenetic modifications in rheumatoid arthritis: Insights from MTX, JAK inhibitors, and LLDT-8

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Authors

JZJianan ZhaoShanghai University of Traditional Chinese Medicine YLYunshen LiShanghai University of Traditional Chinese Medicine RZRunrun ZhangZhejiang Chinese Medical University

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Implication

In vitro transcriptomic study reveals key therapeutic targets and epigenetic changes in rheumatoid arthritis synoviocytes, highlighting candidates like GALNT9 and CCNF.

Key Points

To identify therapeutic gene targets and epigenetic modifications modulated by methotrexate, JAK inhibitors, and (5R)-5-hydroxytriptolide (LLDT-8) in rheumatoid arthritis fibroblast-like synoviocytes.
Isolated primary fibroblast-like synoviocytes (FLS) from synovial tissues of rheumatoid arthritis (RA) and osteoarthritis (OA) patients.
Treated RA FLS with methotrexate (MTX), JAK inhibitors, and LLDT-8, performing RNA sequencing to identify differentially expressed genes (DEGs) and pathway enrichment.
Integrated trend analyses with public methylation (GEO GSE46364) and clinical transcriptomic data (PEAC database) to evaluate target genes.
Identified 5,095 DEGs between RA and OA FLS (3,300 upregulated, 1,795 downregulated); drug treatments induced distinct transcriptomic shifts, yielding 3,795 DEGs with JAK inhibitors, 3,195 with MTX, and 12,993 with LLDT-8.
Identified 45 candidate drug target genes through trend analysis that significantly correlated with clinical indices in RA patients.
Pinpointed GALNT9 and CCNF as key candidates exhibiting concurrent expression and DNA methylation alterations, implicating cell cycle, FoxO, and p53 signaling pathways.

Cite This Study

Zhao et al. (2025) studied this question.

synapsesocial.com/papers/6aaf41bfdc4bef2ee7d062d9 https://doi.org/10.1016/j.bbrep.2025.102038

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Implication

In vitro transcriptomic study reveals key therapeutic targets and epigenetic changes in rheumatoid arthritis synoviocytes, highlighting candidates like GALNT9 and CCNF.

Therapeutic gene targets and epigenetic modifications in rheumatoid arthritis: Insights from MTX, JAK inhibitors, and LLDT-8

Discussion

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Implication

Key Points

Cite This Study

Therapeutic gene targets and epigenetic modifications in rheumatoid arthritis: Insights from MTX, JAK inhibitors, and LLDT-8

Discussion

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Implication

Key Points

Cite This Study

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