PMID- 15292528
OWN - NLM
STAT- MEDLINE
DCOM- 20041221
LR  - 20070906
IS  - 1462-0324 (Print)
IS  - 1462-0324 (Linking)
VI  - 43
IP  - 11
DP  - 2004 Nov
TI  - Detection of differentially expressed genes in synovial fibroblasts by 
      restriction fragment differential display.
PG  - 1346-52
AB  - 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: 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 beta (GRObeta), 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-alpha and IL-1beta. 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-alpha and IL-1. 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.
FAU - Scaife, S
AU  - Scaife S
AD  - Yamanouchi Research Institute, Oxford, UK.
FAU - Brown, R
AU  - Brown R
FAU - Kellie, S
AU  - Kellie S
FAU - Filer, A
AU  - Filer A
FAU - Martin, S
AU  - Martin S
FAU - Thomas, A M C
AU  - Thomas AM
FAU - Bradfield, P F
AU  - Bradfield PF
FAU - Amft, N
AU  - Amft N
FAU - Salmon, M
AU  - Salmon M
FAU - Buckley, C D
AU  - Buckley CD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040803
PL  - England
TA  - Rheumatology (Oxford)
JT  - Rheumatology (Oxford, England)
JID - 100883501
RN  - 0 (Interleukin-6)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Arthritis/*genetics/metabolism
MH  - Arthritis, Rheumatoid/genetics/metabolism
MH  - Cells, Cultured
MH  - Female
MH  - Fibroblasts/*metabolism/pathology
MH  - Gene Expression Regulation
MH  - Humans
MH  - Interleukin-6/biosynthesis
MH  - Male
MH  - Middle Aged
MH  - Osteoarthritis/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction/methods
MH  - Skin/metabolism
MH  - Synovial Membrane/*metabolism/pathology
EDAT- 2004/08/05 05:00
MHDA- 2004/12/22 09:00
CRDT- 2004/08/05 05:00
PHST- 2004/08/05 05:00 [pubmed]
PHST- 2004/12/22 09:00 [medline]
PHST- 2004/08/05 05:00 [entrez]
AID - keh347 [pii]
AID - 10.1093/rheumatology/keh347 [doi]
PST - ppublish
SO  - Rheumatology (Oxford). 2004 Nov;43(11):1346-52. doi: 10.1093/rheumatology/keh347. 
      Epub 2004 Aug 3.