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Invasive properties of fibroblast-like synoviocytes: correlation with growth characteristics and expression of MMP-1, MMP-3, and MMP-10

Background: Matrix metalloproteinases (MMPs) have a pivotal role in the destruction of cartilage in rheumatoid arthritis (RA), which is mediated by the fibroblast-like synoviocytes (FLS). Objective: To examine the in vitro invasiveness of synoviocytes obtained from inflamed joints of patients with a... Full description

Journal Title: Annals of the rheumatic diseases 2002, Vol.61 (11), p.975-980
Main Author: Tolboom, T C A
Other Authors: Pieterman, E , van der Laan, W H , Toes, R E M , Huidekoper, A L , Nelissen, R G H H , Breedveld, F C , Huizinga, T W J
Format: Electronic Article Electronic Article
Language: English
Subjects:
Aged
Arthritis, Rheumatoid - enzymology
Arthritis, Rheumatoid - pathology
avascular necrosis
AVN
Biological and medical sciences
Cathepsin K
Cathepsins - physiology
Cell Culture Techniques
Cell Division
Collagen
connective tissue diseases
Development and progression
Diseases of the osteoarticular system
Drug Combinations
ECM
Enzymes
Extended Report
extracellular matrix
FCS
fetal calf serum
fibroblast-like synoviocytes
Fibroblasts
Fibroblasts - enzymology
Fibroblasts - pathology
FLS
Humans
IMDM
Inflammatory joint diseases
invasion
Investigations
Iscove’s modified Dulbecco’s medium
Laminin
matrix metalloproteinase
Matrix Metalloproteinase 1 - genetics
Matrix Metalloproteinase 1 - metabolism
Matrix Metalloproteinase 2 - genetics
Matrix Metalloproteinase 2 - metabolism
matrix metalloproteinases
Matrix Metalloproteinases - metabolism
Matrix Metalloproteinases - physiology
Medical sciences
Metalloproteins
Middle Aged
MLV-RT
MMP
murine leukaemia virus- reverse transcriptase
musculoskeletal diseases
musculoskeletal system
osteoarthritis
Osteoarthritis - enzymology
Osteoarthritis - pathology
PBS
phosphate buffered saline
Physiological aspects
Principal components analysis
Proteoglycans
reverse transcriptase-polymerase chain reaction
Rheumatoid arthritis
RNA, Messenger - genetics
RT-PCR
skin
Synovial Membrane - pathology
TIMP
tissue inhibitor of matrix metalloproteinase
Tissue Inhibitor of Metalloproteinases - physiology
Quelle: Alma/SFX Local Collection
Publisher: London: BMJ Publishing Group Ltd and European League Against Rheumatism
ID: ISSN: 0003-4967
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recordid: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1753950
title: Invasive properties of fibroblast-like synoviocytes: correlation with growth characteristics and expression of MMP-1, MMP-3, and MMP-10
format: Article
creator:
  • Tolboom, T C A
  • Pieterman, E
  • van der Laan, W H
  • Toes, R E M
  • Huidekoper, A L
  • Nelissen, R G H H
  • Breedveld, F C
  • Huizinga, T W J
subjects:
  • Aged
  • Arthritis, Rheumatoid - enzymology
  • Arthritis, Rheumatoid - pathology
  • avascular necrosis
  • AVN
  • Biological and medical sciences
  • Cathepsin K
  • Cathepsins - physiology
  • Cell Culture Techniques
  • Cell Division
  • Collagen
  • connective tissue diseases
  • Development and progression
  • Diseases of the osteoarticular system
  • Drug Combinations
  • ECM
  • Enzymes
  • Extended Report
  • extracellular matrix
  • FCS
  • fetal calf serum
  • fibroblast-like synoviocytes
  • Fibroblasts
  • Fibroblasts - enzymology
  • Fibroblasts - pathology
  • FLS
  • Humans
  • IMDM
  • Inflammatory joint diseases
  • invasion
  • Investigations
  • Iscove’s modified Dulbecco’s medium
  • Laminin
  • matrix metalloproteinase
  • Matrix Metalloproteinase 1 - genetics
  • Matrix Metalloproteinase 1 - metabolism
  • Matrix Metalloproteinase 2 - genetics
  • Matrix Metalloproteinase 2 - metabolism
  • matrix metalloproteinases
  • Matrix Metalloproteinases - metabolism
  • Matrix Metalloproteinases - physiology
  • Medical sciences
  • Metalloproteins
  • Middle Aged
  • MLV-RT
  • MMP
  • murine leukaemia virus- reverse transcriptase
  • musculoskeletal diseases
  • musculoskeletal system
  • osteoarthritis
  • Osteoarthritis - enzymology
  • Osteoarthritis - pathology
  • PBS
  • phosphate buffered saline
  • Physiological aspects
  • Principal components analysis
  • Proteoglycans
  • reverse transcriptase-polymerase chain reaction
  • Rheumatoid arthritis
  • RNA, Messenger - genetics
  • RT-PCR
  • skin
  • Synovial Membrane - pathology
  • TIMP
  • tissue inhibitor of matrix metalloproteinase
  • Tissue Inhibitor of Metalloproteinases - physiology
ispartof: Annals of the rheumatic diseases, 2002, Vol.61 (11), p.975-980
description: Background: Matrix metalloproteinases (MMPs) have a pivotal role in the destruction of cartilage in rheumatoid arthritis (RA), which is mediated by the fibroblast-like synoviocytes (FLS). Objective: To examine the in vitro invasiveness of synoviocytes obtained from inflamed joints of patients with arthritis in relation to the expression of MMP 1–14, 17, 19, cathepsin-K, the tissue inhibitors of matrix metalloproteinases TIMP-1 and TIMP-2 by FLS. Methods: FLS were derived from 56 patients (30 with RA, 17 with osteoarthritis (OA), and nine with avascular necrosis (AVN)). Invasive growth of FLS through an artificial matrix (Matrigel) was measured in a transwell system. The number of cells that migrated through the matrix were counted. Proliferation rate was determined by counting the FLS after seven days of culturing. Expression of MMPs, cathepsin-K and TIMPs was investigated with reverse transcriptase-polymerase chain reaction and related to the expression of a household gene, β-actin. Results: FLS from RA showed greater invasive growth than FLS from OA and AVN. The median number of cells that grew through the matrix membrane was 4788 for RA, significantly higher than the number for OA, 1875 (p
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0003-4967
fulltext: fulltext
issn:
  • 0003-4967
  • 1468-2060
url: Link


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titleInvasive properties of fibroblast-like synoviocytes: correlation with growth characteristics and expression of MMP-1, MMP-3, and MMP-10
sourceAlma/SFX Local Collection
creatorTolboom, T C A ; Pieterman, E ; van der Laan, W H ; Toes, R E M ; Huidekoper, A L ; Nelissen, R G H H ; Breedveld, F C ; Huizinga, T W J
creatorcontribTolboom, T C A ; Pieterman, E ; van der Laan, W H ; Toes, R E M ; Huidekoper, A L ; Nelissen, R G H H ; Breedveld, F C ; Huizinga, T W J
descriptionBackground: Matrix metalloproteinases (MMPs) have a pivotal role in the destruction of cartilage in rheumatoid arthritis (RA), which is mediated by the fibroblast-like synoviocytes (FLS). Objective: To examine the in vitro invasiveness of synoviocytes obtained from inflamed joints of patients with arthritis in relation to the expression of MMP 1–14, 17, 19, cathepsin-K, the tissue inhibitors of matrix metalloproteinases TIMP-1 and TIMP-2 by FLS. Methods: FLS were derived from 56 patients (30 with RA, 17 with osteoarthritis (OA), and nine with avascular necrosis (AVN)). Invasive growth of FLS through an artificial matrix (Matrigel) was measured in a transwell system. The number of cells that migrated through the matrix were counted. Proliferation rate was determined by counting the FLS after seven days of culturing. Expression of MMPs, cathepsin-K and TIMPs was investigated with reverse transcriptase-polymerase chain reaction and related to the expression of a household gene, β-actin. Results: FLS from RA showed greater invasive growth than FLS from OA and AVN. The median number of cells that grew through the matrix membrane was 4788 for RA, significantly higher than the number for OA, 1875 (p<0.001) and for AVN, 1530 (p=0.014). The median rate of proliferation of RA FLS was 0.27 per day compared with OA 0.22 per day (p= 0.012) and AVN 0.25 per day, but there was no correlation between the rate of proliferation and invasive growth in vitro. FLS from RA and OA that expressed MMP-1, MMP-3, or MMP-10 were significantly more invasive (median number of invasive cells: 3835, 4248, 4990, respectively) than cells that did not express these MMPs (1605, p=0.03; 1970, p=0.004; 2360, p=0.012, respectively). There was also a significant relationship between the expression of MMP-1 and MMP-9 and the diagnosis RA (both p=0.013). The expression levels of mRNA for MMP-1 and MMP-2 correlated with the protein levels produced by the synoviocytes as measured by an enzyme linked immunosorbent assay (ELISA). Conclusion: FLS of RA invade more aggressively in a Matrigel matrix than OA and AVN FLS; this is not because of a higher rate of proliferation of RA FLS. The significant correlation between the expression of MMP-1, MMP-3, and MMP-10 and invasive growth in a Matrigel transwell system suggests that these MMPs play a part in the invasive growth of FLS obtained from patients with RA.
identifier
0ISSN: 0003-4967
1EISSN: 1468-2060
2DOI: 10.1136/ard.61.11.975
3PMID: 12379519
4CODEN: ARDIAO
languageeng
publisherLondon: BMJ Publishing Group Ltd and European League Against Rheumatism
subjectAged ; Arthritis, Rheumatoid - enzymology ; Arthritis, Rheumatoid - pathology ; avascular necrosis ; AVN ; Biological and medical sciences ; Cathepsin K ; Cathepsins - physiology ; Cell Culture Techniques ; Cell Division ; Collagen ; connective tissue diseases ; Development and progression ; Diseases of the osteoarticular system ; Drug Combinations ; ECM ; Enzymes ; Extended Report ; extracellular matrix ; FCS ; fetal calf serum ; fibroblast-like synoviocytes ; Fibroblasts ; Fibroblasts - enzymology ; Fibroblasts - pathology ; FLS ; Humans ; IMDM ; Inflammatory joint diseases ; invasion ; Investigations ; Iscove’s modified Dulbecco’s medium ; Laminin ; matrix metalloproteinase ; Matrix Metalloproteinase 1 - genetics ; Matrix Metalloproteinase 1 - metabolism ; Matrix Metalloproteinase 2 - genetics ; Matrix Metalloproteinase 2 - metabolism ; matrix metalloproteinases ; Matrix Metalloproteinases - metabolism ; Matrix Metalloproteinases - physiology ; Medical sciences ; Metalloproteins ; Middle Aged ; MLV-RT ; MMP ; murine leukaemia virus- reverse transcriptase ; musculoskeletal diseases ; musculoskeletal system ; osteoarthritis ; Osteoarthritis - enzymology ; Osteoarthritis - pathology ; PBS ; phosphate buffered saline ; Physiological aspects ; Principal components analysis ; Proteoglycans ; reverse transcriptase-polymerase chain reaction ; Rheumatoid arthritis ; RNA, Messenger - genetics ; RT-PCR ; skin ; Synovial Membrane - pathology ; TIMP ; tissue inhibitor of matrix metalloproteinase ; Tissue Inhibitor of Metalloproteinases - physiology
ispartofAnnals of the rheumatic diseases, 2002, Vol.61 (11), p.975-980
rights
0Copyright 2002 by Annals of the Rheumatic Diseases
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0Tolboom, T C A
1Pieterman, E
2van der Laan, W H
3Toes, R E M
4Huidekoper, A L
5Nelissen, R G H H
6Breedveld, F C
7Huizinga, T W J
title
0Invasive properties of fibroblast-like synoviocytes: correlation with growth characteristics and expression of MMP-1, MMP-3, and MMP-10
1Annals of the rheumatic diseases
addtitleAnn Rheum Dis
descriptionBackground: Matrix metalloproteinases (MMPs) have a pivotal role in the destruction of cartilage in rheumatoid arthritis (RA), which is mediated by the fibroblast-like synoviocytes (FLS). Objective: To examine the in vitro invasiveness of synoviocytes obtained from inflamed joints of patients with arthritis in relation to the expression of MMP 1–14, 17, 19, cathepsin-K, the tissue inhibitors of matrix metalloproteinases TIMP-1 and TIMP-2 by FLS. Methods: FLS were derived from 56 patients (30 with RA, 17 with osteoarthritis (OA), and nine with avascular necrosis (AVN)). Invasive growth of FLS through an artificial matrix (Matrigel) was measured in a transwell system. The number of cells that migrated through the matrix were counted. Proliferation rate was determined by counting the FLS after seven days of culturing. Expression of MMPs, cathepsin-K and TIMPs was investigated with reverse transcriptase-polymerase chain reaction and related to the expression of a household gene, β-actin. Results: FLS from RA showed greater invasive growth than FLS from OA and AVN. The median number of cells that grew through the matrix membrane was 4788 for RA, significantly higher than the number for OA, 1875 (p<0.001) and for AVN, 1530 (p=0.014). The median rate of proliferation of RA FLS was 0.27 per day compared with OA 0.22 per day (p= 0.012) and AVN 0.25 per day, but there was no correlation between the rate of proliferation and invasive growth in vitro. FLS from RA and OA that expressed MMP-1, MMP-3, or MMP-10 were significantly more invasive (median number of invasive cells: 3835, 4248, 4990, respectively) than cells that did not express these MMPs (1605, p=0.03; 1970, p=0.004; 2360, p=0.012, respectively). There was also a significant relationship between the expression of MMP-1 and MMP-9 and the diagnosis RA (both p=0.013). The expression levels of mRNA for MMP-1 and MMP-2 correlated with the protein levels produced by the synoviocytes as measured by an enzyme linked immunosorbent assay (ELISA). Conclusion: FLS of RA invade more aggressively in a Matrigel matrix than OA and AVN FLS; this is not because of a higher rate of proliferation of RA FLS. The significant correlation between the expression of MMP-1, MMP-3, and MMP-10 and invasive growth in a Matrigel transwell system suggests that these MMPs play a part in the invasive growth of FLS obtained from patients with RA.
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1Arthritis, Rheumatoid - enzymology
2Arthritis, Rheumatoid - pathology
3avascular necrosis
4AVN
5Biological and medical sciences
6Cathepsin K
7Cathepsins - physiology
8Cell Culture Techniques
9Cell Division
10Collagen
11connective tissue diseases
12Development and progression
13Diseases of the osteoarticular system
14Drug Combinations
15ECM
16Enzymes
17Extended Report
18extracellular matrix
19FCS
20fetal calf serum
21fibroblast-like synoviocytes
22Fibroblasts
23Fibroblasts - enzymology
24Fibroblasts - pathology
25FLS
26Humans
27IMDM
28Inflammatory joint diseases
29invasion
30Investigations
31Iscove’s modified Dulbecco’s medium
32Laminin
33matrix metalloproteinase
34Matrix Metalloproteinase 1 - genetics
35Matrix Metalloproteinase 1 - metabolism
36Matrix Metalloproteinase 2 - genetics
37Matrix Metalloproteinase 2 - metabolism
38matrix metalloproteinases
39Matrix Metalloproteinases - metabolism
40Matrix Metalloproteinases - physiology
41Medical sciences
42Metalloproteins
43Middle Aged
44MLV-RT
45MMP
46murine leukaemia virus- reverse transcriptase
47musculoskeletal diseases
48musculoskeletal system
49osteoarthritis
50Osteoarthritis - enzymology
51Osteoarthritis - pathology
52PBS
53phosphate buffered saline
54Physiological aspects
55Principal components analysis
56Proteoglycans
57reverse transcriptase-polymerase chain reaction
58Rheumatoid arthritis
59RNA, Messenger - genetics
60RT-PCR
61skin
62Synovial Membrane - pathology
63TIMP
64tissue inhibitor of matrix metalloproteinase
65Tissue Inhibitor of Metalloproteinases - physiology
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11468-2060
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2van der Laan, W H
3Toes, R E M
4Huidekoper, A L
5Nelissen, R G H H
6Breedveld, F C
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titleInvasive properties of fibroblast-like synoviocytes: correlation with growth characteristics and expression of MMP-1, MMP-3, and MMP-10
authorTolboom, T C A ; Pieterman, E ; van der Laan, W H ; Toes, R E M ; Huidekoper, A L ; Nelissen, R G H H ; Breedveld, F C ; Huizinga, T W J
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1Arthritis, Rheumatoid - enzymology
2Arthritis, Rheumatoid - pathology
3avascular necrosis
4AVN
5Biological and medical sciences
6Cathepsin K
7Cathepsins - physiology
8Cell Culture Techniques
9Cell Division
10Collagen
11connective tissue diseases
12Development and progression
13Diseases of the osteoarticular system
14Drug Combinations
15ECM
16Enzymes
17Extended Report
18extracellular matrix
19FCS
20fetal calf serum
21fibroblast-like synoviocytes
22Fibroblasts
23Fibroblasts - enzymology
24Fibroblasts - pathology
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27IMDM
28Inflammatory joint diseases
29invasion
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32Laminin
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34Matrix Metalloproteinase 1 - genetics
35Matrix Metalloproteinase 1 - metabolism
36Matrix Metalloproteinase 2 - genetics
37Matrix Metalloproteinase 2 - metabolism
38matrix metalloproteinases
39Matrix Metalloproteinases - metabolism
40Matrix Metalloproteinases - physiology
41Medical sciences
42Metalloproteins
43Middle Aged
44MLV-RT
45MMP
46murine leukaemia virus- reverse transcriptase
47musculoskeletal diseases
48musculoskeletal system
49osteoarthritis
50Osteoarthritis - enzymology
51Osteoarthritis - pathology
52PBS
53phosphate buffered saline
54Physiological aspects
55Principal components analysis
56Proteoglycans
57reverse transcriptase-polymerase chain reaction
58Rheumatoid arthritis
59RNA, Messenger - genetics
60RT-PCR
61skin
62Synovial Membrane - pathology
63TIMP
64tissue inhibitor of matrix metalloproteinase
65Tissue Inhibitor of Metalloproteinases - physiology
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5Nelissen, R G H H
6Breedveld, F C
7Huizinga, T W J
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0Tolboom, T C A
1Pieterman, E
2van der Laan, W H
3Toes, R E M
4Huidekoper, A L
5Nelissen, R G H H
6Breedveld, F C
7Huizinga, T W J
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atitleInvasive properties of fibroblast-like synoviocytes: correlation with growth characteristics and expression of MMP-1, MMP-3, and MMP-10
jtitleAnnals of the rheumatic diseases
addtitleAnn Rheum Dis
date2002-11
risdate2002
volume61
issue11
spage975
epage980
pages975-980
issn0003-4967
eissn1468-2060
codenARDIAO
notesCorrespondence to:
 Professor T W J Huizinga, Leiden University Medical Centre, Department of Rheumatology, C4-R, PO Box 9600, 2300 RC Leiden, The Netherlands;
 T.W.J.Huizinga@LUMC.nl
abstractBackground: Matrix metalloproteinases (MMPs) have a pivotal role in the destruction of cartilage in rheumatoid arthritis (RA), which is mediated by the fibroblast-like synoviocytes (FLS). Objective: To examine the in vitro invasiveness of synoviocytes obtained from inflamed joints of patients with arthritis in relation to the expression of MMP 1–14, 17, 19, cathepsin-K, the tissue inhibitors of matrix metalloproteinases TIMP-1 and TIMP-2 by FLS. Methods: FLS were derived from 56 patients (30 with RA, 17 with osteoarthritis (OA), and nine with avascular necrosis (AVN)). Invasive growth of FLS through an artificial matrix (Matrigel) was measured in a transwell system. The number of cells that migrated through the matrix were counted. Proliferation rate was determined by counting the FLS after seven days of culturing. Expression of MMPs, cathepsin-K and TIMPs was investigated with reverse transcriptase-polymerase chain reaction and related to the expression of a household gene, β-actin. Results: FLS from RA showed greater invasive growth than FLS from OA and AVN. The median number of cells that grew through the matrix membrane was 4788 for RA, significantly higher than the number for OA, 1875 (p<0.001) and for AVN, 1530 (p=0.014). The median rate of proliferation of RA FLS was 0.27 per day compared with OA 0.22 per day (p= 0.012) and AVN 0.25 per day, but there was no correlation between the rate of proliferation and invasive growth in vitro. FLS from RA and OA that expressed MMP-1, MMP-3, or MMP-10 were significantly more invasive (median number of invasive cells: 3835, 4248, 4990, respectively) than cells that did not express these MMPs (1605, p=0.03; 1970, p=0.004; 2360, p=0.012, respectively). There was also a significant relationship between the expression of MMP-1 and MMP-9 and the diagnosis RA (both p=0.013). The expression levels of mRNA for MMP-1 and MMP-2 correlated with the protein levels produced by the synoviocytes as measured by an enzyme linked immunosorbent assay (ELISA). Conclusion: FLS of RA invade more aggressively in a Matrigel matrix than OA and AVN FLS; this is not because of a higher rate of proliferation of RA FLS. The significant correlation between the expression of MMP-1, MMP-3, and MMP-10 and invasive growth in a Matrigel transwell system suggests that these MMPs play a part in the invasive growth of FLS obtained from patients with RA.
copLondon
pubBMJ Publishing Group Ltd and European League Against Rheumatism
pmid12379519
doi10.1136/ard.61.11.975
oafree_for_read