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Inflammation Research

, Volume 62, Issue 2, pp 229–237 | Cite as

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

  • Ke Xu
  • Peng Xu
  • Jian-Feng Yao
  • Yin-Gang Zhang
  • Wei-kun Hou
  • She-Min Lu
Original Research Paper

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.

Keywords

Rheumatoid arthritis Osteoarthritis Autophagy Apoptosis Synovium 

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

Notes

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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Copyright information

© Springer Basel 2012

Authors and Affiliations

  1. 1.Department of Joint Surgery, Hong Hui HospitalXi’an Jiaotong University College of MedicineXi’anChina
  2. 2.Department of OrthopedicsFirst Affiliated Hospital of Xi’an Jiaotong University College of MedicineXi’anChina
  3. 3.Department of Genetics and Molecular BiologyXi’an Jiaotong University College of MedicineXi’anChina

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