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Journal of Bone and Mineral Metabolism

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12-08-2022 | Rheumatoid Arthritis | Original Article

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

Authors: Tao Cheng, Jian Wu, Yaozeng Xu, Cuiping Liu, Huayong Zhang, Mingjun Wang

Published in: Journal of Bone and Mineral Metabolism | Issue 5/2022

Abstract

Introduction

A genome-wide association analysis revealed a rheumatoid arthritis (RA)-risk-associated genetic locus on chromosome 9, which contained the tumor necrosis factor receptor-associated factor 1 (TRAF1). However, the detail mechanism by TRAF1 signaled to fibroblast-like synoviocytes (FLSs) apoptosis remains to be fully understood.

Materials and methods

Synovial tissue of 10 RA patients and osteoarthritis patients were obtained during joint replacement surgery. We investigated TRAF1 level and FLSs apoptosis percentage in vivo and elucidated the mechanism involved in the regulation of apoptotic process in vitro.

Results

We proved the significant increase of TRAF1 level in FLSs of RA patients and demonstrated that TRAF1 level correlated positively with DAS28 score and negatively with FLSs apoptosis. Treatment with siTRAF1 was able to decrease MMPs levels and the phosphorylated forms of JNK/NF-κB in vitro. Moreover, JNK inhibitor could attenuate expression of MMPs and increase percentage of apoptosis in RA-FLSs, while siTRAF1 could not promote apoptosis when RA-FLSs were pretreated with JNK activator.

Conclusions

High levels of TRAF1 in RA synovium play an important role in the synovial hyperplasia of RA by suppressing apoptosis through activating JNK/NF-kB-dependent signaling pathways in response to the engagement of CD40.

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Title: CD40/TRAF1 decreases synovial cell apoptosis in patients with rheumatoid arthritis through JNK/NF-κB pathway
Authors: Tao Cheng
Jian Wu
Yaozeng Xu
Cuiping Liu
Huayong Zhang
Mingjun Wang
Publication date: 12-08-2022
Publisher: Springer Nature Singapore
Keyword: Rheumatoid Arthritis
Published in: Journal of Bone and Mineral Metabolism / Issue 5/2022
Print ISSN: 0914-8779
Electronic ISSN: 1435-5604
DOI: https://doi.org/10.1007/s00774-022-01350-6

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

Abstract

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Materials and methods

Results

Conclusions

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Conclusions

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