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Updated: Sep 1, 2025

An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
07:37

An Adoptive Transfer Model of Rheumatoid Arthritis in Mice

Published on: June 6, 2025

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CD40/TRAF1 decreases synovial cell apoptosis in patients with rheumatoid arthritis through JNK/NF-κB pathway

Tao Cheng1, Jian Wu2, Yaozeng Xu3

  • 1Department of Rheumatology, The First Affiliated Hospital of Soochow University, Suzhou, 215000, China. chengtao0526@126.com.

Journal of Bone and Mineral Metabolism
|August 12, 2022
PubMed
Abstract

Insights

High tumor necrosis factor receptor-associated factor 1 (TRAF1) levels in rheumatoid arthritis (RA) synovium suppress fibroblast-like synoviocytes (FLSs) apoptosis. This process involves activating JNK/NF-κB signaling pathways, contributing to synovial hyperplasia in RA.

Area of Science:

  • Immunology
  • Genetics
  • Molecular Biology

Background:

  • Rheumatoid arthritis (RA) risk is linked to a genetic locus on chromosome 9 containing the tumor necrosis factor receptor-associated factor 1 (TRAF1) gene.
  • The precise mechanisms by which TRAF1 influences apoptosis in fibroblast-like synoviocytes (FLSs) in RA remain unclear.

Purpose of the Study:

  • To investigate the role of TRAF1 in RA pathogenesis.
  • To elucidate the signaling pathways through which TRAF1 affects FLS apoptosis.

Main Methods:

  • Analysis of TRAF1 levels and FLS apoptosis in synovial tissues from RA and osteoarthritis patients.
  • In vitro experiments using small interfering RNA (siRNA) targeting TRAF1 and JNK inhibitors in RA-FLSs.

Main Results:

  • TRAF1 levels were significantly increased in RA FLSs and correlated positively with disease activity (DAS28 score) and negatively with FLS apoptosis.
  • Reducing TRAF1 levels decreased matrix metalloproteinases (MMPs) and phosphorylated JNK/NF-κB.
  • JNK inhibition increased apoptosis and decreased MMPs, while TRAF1 knockdown failed to induce apoptosis in the presence of JNK activators.

Conclusions:

  • Elevated TRAF1 in RA synovium promotes synovial hyperplasia by inhibiting FLS apoptosis.
  • This inhibition occurs via the activation of JNK/NF-κB signaling pathways, particularly in response to CD40 engagement.
Keywords:
ApoptosisJNK/NF-κBRheumatoid arthritisTRAF1

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