Rheumatology Advance Access published online on August 3, 2004
Rheumatology, doi:10.1093/rheumatology/keh347
Rheumatology © British Society for Rheumatology 2004; all rights reserved
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1 Yamanouchi Research Institute, Oxford, UK
* To whom correspondence should be addressed. E-mail: c.d.buckley{at}bham.ac.uk.
Objective. To identify differentially expressed genes in synovial fibroblasts and examine the effect on gene expression of exposure to TNF- Methods. Restriction fragment differential display was used to isolate genes using degenerate primers complementary to the lysophosphatidic acid acyl transferase gene family. Differential gene expression was confirmed by reverse transcription-polymerase chain reaction and immunohistochemistry using a variety of synovial fibroblasts, including cells from patients with osteoarthritis and self-limiting parvovirus arthritis. Results. Irrespective of disease process, synovial fibroblasts constitutively produced higher levels of IL-6 and monocyte chemoattractant protein 1 (MCP-1) (CCL2) than skin fibroblasts. Seven genes were differentially expressed in synovial fibroblasts compared with skin fibroblasts. Of these genes, four [tissue factor pathway inhibitor 2 (TFPI2), growth regulatory oncogene Conclusions. Seven genes have been identified with differential expression patterns in terms of disease process (osteoarthritis vs rheumatoid arthritis), state of activation (resting vs cytokine activation) and anatomical location (synovium vs skin). Four of these genes, TFPI2, GRO
Accepted June 29, 2004
Original Papers
Detection of differentially expressed genes in synovial fibroblasts by restriction fragment differential display
2 Yamanouchi Research Institute, Oxford, UK; Present address: School of Molecular and Microbial Sciences and Institute of Molecular Biosciences/CRC for Chronic Inflammatory Diseases, University of Queensland, St Lucia, Brisbane, Qld 4072, Australia
3 Department of Rheumatology, Division of Immunity and Infection, University of Birmingham, Birmingham, UK
4 Royal Orthopaedic Hospital NHS Trust, Birmingham, UK
Abstract 
and IL-1
. (GRO), manganese superoxide dismutase (MnSOD) and granulocyte chemotactic protein 2 (GCP-2)] were all found to be constitutively overexpressed in synoviocytes derived from patients with osteoarthritis. These four genes were only weakly expressed in other synovial fibroblasts (rheumatoid and self-limiting parvovirus infection). However, expression in all types of fibroblasts was increased after stimulation with TNF- and IL-1. Three other genes (aggrecan, biglycan and caldesmon) were expressed at higher levels in all types of synovial fibroblasts compared with skin fibroblasts even after stimulation with TNF- and IL-1. (CXCL2), MnSOD and GCP-2 (CXCL6), were selectively overexpressed in osteoarthritis fibroblasts rather than rheumatoid fibroblasts. While these differences may represent differential behaviour of synovial fibroblasts in in vitro culture, these observations suggest that TFPI2, GRO (CXCL2), MnSOD and GCP-2 (CXCL6) may represent new targets for treatments specifically tailored to osteoarthritis.
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