Vol.22 No.2

Original Article

Regenerating gene (REG) 1 alpha promotes pannus progression in patients with rheumatoid arthritis

Authors

Maki Fujishiro1 , Kazuhisa Nozawa1,2 , Mikiko Kawasaki1 , Ayako Yamaguchi1,2 , Kazuhisa Iwabuchi1 , Mitsuaki Yanagida1 , Fujihiko Suzuki3 , Keiji Miyazawa4 , Hirokazu Fukui5 , Kazuo Kaneko6 , Hideoki Ogawa1 , Kenji Takamori1, Yoshinari Takasaki2, Iwao Sekigawa1,7

  • Institute for Environment and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan
  • Department of Rheumatology, School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
  • Department of Pathology, Juntendo University Urayasu Hospital, Chiba, Japan
  • Central Research Laboratories, Kissei Pharmaceutical Co. Ltd, Azumino, Nagano, Japan
  • Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
  • Department of Orthopaedics, School of Medicine, Juntendo University, Tokyo, Japan
  • Department of Internal Medicine and Rheumatology, Juntendo University Urayasu Hospital, Chiba, Japan
Received:

19 August 2010

Accepted:

30 June 2011

Published online:

28 December 2011

Full Text

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Abstract

Introduction A protein analysis using mass spectrometry revealed the existence of serum proteins with significant quantitative changes after the administration of infliximab. Among these proteins, regenerating gene (REG) 1α appears to be related to the pathogenesis of rheumatoid arthritis (RA). Therefore, the present study was conducted to examine the mechanism of REG1α in RA disease progression.
Methods Serum samples were collected from RA patients and normal healthy controls. REG1α expression was evaluated by ELISA, RT-PCR, and indirect immunofluorescence microscopy. The functions of REG1α on synovial fibroblasts with regard to apoptosis, receptor activator of NF-κB ligand (RANKL) expression, and cellar proliferation were evaluated using siRNA to inhibit the intrinsic REG1a mRNA expression.
Results The serum concentrations of REG1α in RA patients were higher than in normal healthy controls. The high expression of REG1α was also observed in the synovial tissue of RA patients compared to those of osteoarthropathy patients. In addition, tumor necrosis factor-α (TNF-α) upregulated REG1α expression in the synovial fibroblasts cell line (MH7A). Inhibition of REG1α expression suppressed the induction of RANKL expression by TNF-α. Furthermore, exogenous recombinant REG1α protein inhibited apoptosis and promoted cell proliferation in MH7A cells. These effects were abolished in the REG1α-siRNA MH7A cells.
Conclusion The present data suggest that TNF-α induces aberrant REG1α expression and that REG1α plays an important role in aberrant cell proliferation and RANKL expression of synovial fibroblasts, ultimately resulting in pannus formation. Restoration of normal physiological REG1α expression may contribute to disease amelioration.

Key words

Rheumatoid arthritis - Human - Inflammation