Abstract | OBJECTIVE: To identify differentially expressed genes in synovial fibroblasts and examine the effect on gene expression of exposure to TNF-alpha and IL-1beta. 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: 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, GRObeta (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, GRObeta (CXCL2), MnSOD and GCP-2 (CXCL6) may represent new targets for treatments specifically tailored to osteoarthritis.
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Authors | S Scaife, R Brown, S Kellie, A Filer, S Martin, A M C Thomas, P F Bradfield, N Amft, M Salmon, C D Buckley |
Journal | Rheumatology (Oxford, England)
(Rheumatology (Oxford))
Vol. 43
Issue 11
Pg. 1346-52
(Nov 2004)
ISSN: 1462-0324 [Print] England |
PMID | 15292528
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Arthritis
(genetics, metabolism)
- Arthritis, Rheumatoid
(genetics, metabolism)
- Cells, Cultured
- Female
- Fibroblasts
(metabolism, pathology)
- Gene Expression Regulation
- Humans
- Interleukin-6
(biosynthesis)
- Male
- Middle Aged
- Osteoarthritis
(genetics, metabolism)
- Reverse Transcriptase Polymerase Chain Reaction
(methods)
- Skin
(metabolism)
- Synovial Membrane
(metabolism, pathology)
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