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Reduced apoptosis correlates with enhanced autophagy in synovial tissues of rheumatoid arthritis

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Abstract

Objective

Defective apoptosis contributes to the massive synovial hyperplasia in rheumatoid arthritis (RA), but the mechanism is largely unknown. To investigate the reasons for the reduced apoptosis in RA synovium, we analyzed autophagy and its relationship to apoptosis in synovial tissues from RA and osteoarthritis (OA) patients.

Methods

Synovial tissues were obtained from seven RA and 12 OA patients undergoing knee replacement surgery. Apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and staining for p85 fragment of PolyADP-ribose polymerase (PARP). Autophagy was determined by immunoblotting for the autophagic markers Beclin-1 and LC3. MicroRNA-30a (miR-30a), which targets Beclin-1, was measured by real-time RT-PCR. The interplay between autophagy and apoptosis was determined via Spearman’s correlation analysis.

Results

In comparison with OA, the synovial tissues from RA displayed decreased TUNEL-positive nuclei (P < 0.01). In contrast, Beclin-1 and LC3 were overexpressed in the synovial lining layers of RA, which was correlated with decreased levels of miR-30a. Moreover, there was a significant reverse relationship between apoptosis and autophagy in RA synovial tissues (P < 0.01 and r = −0.8937).

Conclusion

The impaired apoptosis in RA synovium might result from increased autophagy, which in turn could be due to the deregulation of miRNA-30a.

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Abbreviations

H&E:

Hematoxylin–eosin

OA:

Osteoarthritis

OD:

Optical density

PARP:

PolyADP-ribose polymerase

RA:

Rheumatoid arthritis

SF:

Synovial fibroblast

TBST:

Tris-buffered saline with Tween 20

TUNEL:

Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling

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Acknowledgments

We thank Jianbing Ma and Yumin Zhang for the collection of specimens. This study was supported by the National Natural Science Foundation of China (No. 81171742) and Shaanxi Province Science and Technology Projects (No. 2008K-38).

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Joint Surgery, Hong Hui Hospital, Xi’an Jiaotong University College of Medicine, Xi’an, 710054, China

    Ke Xu, Peng Xu, Jian-Feng Yao & Wei-kun Hou

  2. Department of Orthopedics, First Affiliated Hospital of Xi’an Jiaotong University College of Medicine, Xi’an, 710061, China

    Yin-Gang Zhang

  3. Department of Genetics and Molecular Biology, Xi’an Jiaotong University College of Medicine, Xi’an, 710061, China

    She-Min Lu

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  1. Ke Xu
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  2. Peng Xu
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Correspondence to Peng Xu or She-Min Lu.

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Responsible Editor: John Di Battista.

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Xu, K., Xu, P., Yao, JF. et al. Reduced apoptosis correlates with enhanced autophagy in synovial tissues of rheumatoid arthritis. Inflamm. Res. 62, 229–237 (2013). https://doi.org/10.1007/s00011-012-0572-1

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  • DOI: https://doi.org/10.1007/s00011-012-0572-1

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