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

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Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

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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Funding

This work was supported by Suzhou Minsheng science and technology project (SYS2020108, SYS2019043).

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Author notes

  1. Tao Cheng and Jian Wu contributed equally to this work.

Authors and Affiliations

  1. Department of Rheumatology, The First Affiliated Hospital of Soochow University, Suzhou, 215000, China

    Tao Cheng, Jian Wu, Cuiping Liu & Mingjun Wang

  2. Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, 215000, China

    Yaozeng Xu

  3. Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, China

    Huayong Zhang

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  1. Tao Cheng
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Contributions

TC and JW participated in study design, data collection, data analysis, data interpretation, and drafting the paper. MW, YX, CL and HZ participated in patient recruitment, experiments, and data collection. TC and MW supervised the whole research, designed the study, interpreted the data, and wrote the paper. All the authors contributed to the article and approved the submitted version.

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Correspondence to Tao Cheng or Mingjun Wang.

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Cheng, T., Wu, J., Xu, Y. et al. CD40/TRAF1 decreases synovial cell apoptosis in patients with rheumatoid arthritis through JNK/NF-κB pathway. J Bone Miner Metab 40, 819–828 (2022). https://doi.org/10.1007/s00774-022-01350-6

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