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Involvement of PDCD5 in the regulation of apoptosis in fibroblast-like synoviocytes of rheumatoid arthritis

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Abstract

Apoptosis is reduced in the synovial tissue of patients with rheumatoid arthritis (RA), possibly due to decreased expression of pro-apoptotic genes. Programmed Cell Death 5 (PDCD5) has been recently identified as a protein that mediates apoptosis. Although PDCD5 is down-regulated in many human tumors, the role of PDCD5 in RA has not been investigated. Here we report that reduced levels of PDCD5 mRNA and protein are detected in RA synovial tissue (ST) and fibroblast-like synoviocytes (FLS) than in tissue and cells from patients with osteoarthritis (OA). We also report differences in the PDCD5 expression pattern in tissues from patients with these two types of arthritis. PDCD5 showed a scattered pattern in rheumatoid synovium compared with OA, in which the protein labeling was stronger in the synovial lining layer than in the sublining. We also observed increased expression and nuclear translocation of PDCD5 in RA patient-derived FLS undergoing apoptosis. Finally, overexpression of PDCD5 led to enhanced apoptosis and activation of caspase-3 in triptolide-treated FLS. We propose that PDCD5 may be involved in the pathogenesis of RA. These data also suggest that PDCD5 may serve as a therapeutic target to enhance sensitivity to antirheumatic drug-induced apoptosis in RA.

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Acknowledgments

This work was supported by grants from the National Basic Research Program (973 Program, 2002CB513000) and the National Natural Science Foundation of China (30470844). The authors thank Prof. Da-Long Ma (Peking University, Beijing) for advice and guidance. Conflict of Interest: The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Arthritis Institute, People’s Hospital, Peking University, Beijing, 100044, P.R. China

    Ning Wang, Hou-Shan Lu, Zhen-Peng Guan, Tie-Zheng Sun, Zhan-Kun Chen, Jun Jiang & Chu-Jie Bai

  2. Center for Human Disease Genomics, Peking University, Beijing, 100083, P.R. China

    Ying-Yu Chen

  3. Institute of Hematology, People’s Hospital, Peking University, Beijing, 100044, P.R. China

    Guo-Rui Ruan

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  1. Ning Wang
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Correspondence to Hou-Shan Lu.

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Wang, N., Lu, HS., Guan, ZP. et al. Involvement of PDCD5 in the regulation of apoptosis in fibroblast-like synoviocytes of rheumatoid arthritis. Apoptosis 12, 1433–1441 (2007). https://doi.org/10.1007/s10495-007-0070-z

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  • DOI: https://doi.org/10.1007/s10495-007-0070-z

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