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This article is part of the supplement: Proceedings of the 8th Global Arthritis Research Network (GARN) Meeting and 1st Bio-Rheumatology International Congress (BRIC)

Poster presentation

SPACIA1/SAAL1: a newly identified gene associated with aberrant proliferation of synovial fibroblasts

Tomoo Sato1, Ryoji Fujii1*, Koji Konomi2, Naoko Yagishita1, Satoko Aratani13, Natsumi Araya1, Hiroyuki Aono2, Kazuo Yudoh1, Noboru Suzuki1, Moroe Beppu1, Yoshihisa Yamano1, Kusuki Nishioka3 and Toshihiro Nakajima134

  • * Corresponding author: Ryoji Fujii

Author Affiliations

1 St. Marianna University School of Medicine, Kawasaki, Japan

2 Santen Pharmaceutical Co., Ltd., Osaka, Japan

3 Institute of Medical Science, Tokyo Medical University, Tokyo, Japan

4 Misato Marine Hospital, Kochi, Japan

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Arthritis Research & Therapy 2012, 14(Suppl 1):P61  doi:10.1186/ar3662

The electronic version of this article is the complete one and can be found online at: http://arthritis-research.com/content/14/S1/P61


Published:9 February 2012

© 2012 Sato et al.; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background

The bone and cartilage destruction seen inrheumatoid arthritis (RA) is caused by synovial pannus formation, which is characterized by aberrant proliferation of synovial fibroblasts. Inhibition of synovial proliferation has recently been reported to be a promising therapeutic strategy for RA.However, the specific mechanism underlyingdysregulated proliferation of synovial fibroblasts remains unclear.

Objective

We aimed toidentify and characterize genesthat are involved in the aberrant proliferation of synovial fibroblasts.

Methods

Microarray analysiswas performed to identifythe genes that had upregulated expression inmice with collagen-induced arthritis (CIA). The effect of candidate genes on the proliferation of synovial fibroblasts was screened using antisense oligodeoxynucleotides and small interfering RNAs (siRNAs).

Results

We identified a novel gene named SPACIA1/SAAL1 (synoviocyte proliferation-associated in CIA 1/serum amyloid A-like 1)that was associated with aberrant proliferation of synovial fibroblasts. Immunohistochemicalanalysis indicated that SPACIA1/SAAL1 was strongly expressed in the foot joints of mice with CIA and in the thickened synovial lining of the human RA synovium. Transfection of siRNA targeting SPACIA1/SAAL1into RA synovial fibroblastscould inhibit tumor necrosis factor (TNF)α-induced proliferation more effectively thanit could inhibit serum-induced proliferation.In addition,the antiproliferative effect of SPACIA1/SAAL1 siRNA was caused byinhibition of cell cycle progression and not by induction of apoptosis.We established transgenic (Tg) mice that overexpressed SPACIA1/SAAL1. These Tg mice did not spontaneously develop arthritis or cancer. However,inducing CIA causedgreatersynovial proliferation and worse diseasein Tg mice thanin wild-type mice.

Conclusion

SPACIA1/SAAL1 plays an important role in the aberrant proliferation of synovial fibroblasts under inflammatory conditions.