Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 2/2000

Open Access 01-02-2000 | Research article

Active synovial matrix metalloproteinase-2 is associated with radiographic erosions in patients with early synovitis

Authors: Raphaela Goldbach-Mansky, Jennifer M Lee, Joseph M Hoxworth, David Smith II, Paul Duray, H Ralph Schumacher Jr, Cheryl H Yarboro, John Klippel, David Kleiner, Hani S El-Gabalawy

Published in: Arthritis Research & Therapy | Issue 2/2000

Login to get access

Statement of findings

Serum and synovial tissue expression of the matrix metalloproteinase (MMP)-2 and -9 and their molecular regulators, MMP-14 and TIMP-2 was examined in 28 patients with inflammatory early synovitis and 4 healthy volunteers and correlated with the presence of erosions in the patients. Immunohistological staining of MMP-2, MMP-14 and TIMP-2 localized to corresponding areas in the synovial lining layer and was almost absent in normal synovium. Patients with radiographic erosions had significantly higher levels of active MMP-2 than patients with no erosions, suggesting that activated MMP-2 levels in synovial tissue may be a marker for a more aggressive synovial lesion.
Literature
1.
Suarez-Almazor ME, Soskolne CL, Saunders LD, Russell AS: Outcome in rheumatoid arthritis. A 1985 inception cohort study. J Rheumatol. 1994, 21: 1438-1446.PubMed
2.
Wolfe F: The natural history of rheumatoid arthritis. J Rheumatol. 1996, 23: 13-22.
3.
Emery P: Therapeutic approaches for early rheumatoid arthritis. How early? How aggressive?. Br J Rheum. 1995, 34: 87-90.CrossRef
4.
Zvaifler NJ, Firestein GS: Pannus and pannocytes. Alternative models of joint destruction in rheumatoid arthritis. Arthritis Rheum. 1994, 37: 783-789.PubMedCrossRef
5.
Vincenti MP, Clark IM, Brinckerhoff CE: Using inhibitors of metallo-proteinases to treat arthritis. Easier said than done? [see comments]. Arthritis Rheum. 1994, 37: 1115-1126.PubMedCrossRef
6.
Lindy O, Konttinen YT, Sorsa T: Matrix metalloproteinase 13 (collagenase 3) in human rheumatoid synovium. Arthritis Rheum. 1997, 40: 1391-1399.PubMedCrossRef
7.
Zucker S, Lysik RM, Zarrabi MH: Elevated plasma stromelysin levels in arthritis. J Rheumatol. 1994, 21: 2329-2333.PubMed
8.
Gaudin P, Razakaboay M, Surla A: A study of metalloproteinases in fifty joint fluid specimens. Rev Rhum Engl Ed. 1997, 64: 375-381.PubMed
9.
Ishiguro N, Ito T, Obata K, Fujimoto N, Iwata H: Determination of stromelysin-1, 72 and 92 kDa type IV collagenase, tissue inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2 in synovial fluid and serum from patients with rheumatoid arthritis. J Rheumatol. 1996, 23: 1599-1604.PubMed
10.
Ishiguro N, Ito T, Miyazaki K, Iwata H: Matrix metalloproteinases, tissue inhibitors of metalloproteinases, and glycosaminoglycans in synovial fluid from patients with rheumatoid arthritis. J Rheumatol. 1999, 26: 34-40.PubMed
11.
Ahrens D, Koch AE, Pope RM, Stein-Picarella M, Niedbala MJ: Expression of matrix metalloproteinase 9 (96-kd gelatinase B) in human rheumatoid arthritis. Arthritis Rheum. 1996, 39: 1576-1587.PubMedCrossRef
12.
Gruber BL, Sorbi D, French DL: Markedly elevated serum MMP-9 (gelatinase B) levels in rheumatoid arthritis: a potentially useful laboratory marker. Clin Immunol Immunopathol. 1996, 78: 161-171. 10.1006/clin.1996.0025.PubMedCrossRef
13.
Sopata I, Wize J, Filipowicz-Sosnowska A: Neutrophil gelatinase levels in plasma and synovial fluid of patients with rheumatic diseases. Rheumatol Int. 1995, 15: 9-14.PubMedCrossRef
14.
Konttinen YT, Ceponis A, Takagi M: New collagenolytic enzymes/cascade identified at the pannus-hard tissue junction in rheumatoid arthritis: destruction from above. Matrix Biol. 1998, 17: 585-601.PubMedCrossRef
15.
Cockett MI, Murphy G, Birch ML: Matrix metalloproteinases and metastatic cancer. Biochem Soc Symp. 1998, 63: 295-313.PubMed
16.
Kleiner DE, Stetler-Stevenson WG: Matrix metalloproteinases and metastasis. Cancer Chem Pharmacol. 1999, 43 (suppl): S42-S51.CrossRef
17.
Moses MA: The regulation of neovascularization of matrix metalloproteinases and their inhibitors. Stem Cells. 1997, 15: 180-189.PubMedCrossRef
18.
Wojtowicz-Praga SM, Dickson RB, Hawkins MJ: Matrix metalloproteinase inhibitors. Invest New Drugs. 1997, 15: 61-75.PubMedCrossRef
19.
Borden P, Heller RA: Transcriptional control of matrix metalloproteinases and the tissue inhibitors of matrix metalloproteinases. Crit Rev Eukaryot Gene Expr. 1997, 7: 159-178.PubMedCrossRef
20.
Kleiner DE, Stetler-Stevenson WG: Quantitative zymography: detection of picogram quantities of gelatinases. Anal Biochem . 1994, 218: 325-329. 10.1006/abio.1994.1186.PubMedCrossRef
21.
Arnett FC, Edworthy SM, Bloch DA: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988, 31: 315-324.PubMedCrossRef
22.
Dougados M, van der Linden S, Juhlin R: The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy [see comments]. Arthritis Rheum. 1991, 34: 1218-1227.PubMedCrossRef
23.
Saaibi DL, Schumacher HRJ: Percutaneous needle biopsy and synovial histology. Baillieres Clin Rheumatol. 1996, 10: 535-554.PubMedCrossRef
24.
El-Gabalawy HS, Gallatin M, Vazeux R, Peterman G, Wilkins J: Expression of ICAM-R (ICAM-3), a novel counter-receptor for LFA-1, in rheumatoid and nonrheumatoid synovium. Comparison with other adhesion molecules. Arthritis Rheum. 1994, 37: 846-854.PubMedCrossRef
25.
McQueen FM, Stewart N, Crabbe J: Magnetic resonance imaging of the wrist in early rheumatoid arthritis reveals progression of erosions despite clinical improvement. Ann Rheum Dis. 1999, 58: 156-163.PubMedPubMedCentralCrossRef
26.
Muller-Ladner U, Kriegsmann J, Franklin BN: Synovial fibroblasts of patients with rheumatoid arthritis attach to and invade normal human cartilage when engrafted into SCID mice. Am J Pathol. 1996, 149: 1607-1615.PubMedPubMedCentral
27.
Tarlton JF, Vickery CJ, Leaper DJ, Bailey AJ: Postsurgical wound progression monitored by temporal changes in the expression of matrix metalloproteinase-9. Br J Dermatol. 1997, 137: 506-516.PubMedCrossRef
28.
Unemori EN, Hibbs MS, Amento EP: Constitutive expression of a 92-kD gelatinase (type V collagenase) by rheumatoid synovial fibroblasts and its induction in normal human fibroblasts by inflammatory cytokines. J Clin Invest. 1991, 88: 1656-1662.PubMedPubMedCentralCrossRef
29.
He C: Molecular mechanism of transcriptional activation of human gelatinase B by proximal promoter. Cancer Lett. 1996, 106: 185-191.PubMedCrossRef
30.
Werb Z, Mainardi CL, Vater CA, Harris EDJ: Endogenous activiation of latent collagenase by rheumatoid synovial cells. Evidence for a role of plasminogen activator. N Engl J Med. 1977, 296: 1017-1023.PubMedCrossRef
31.
Blaser J, Triebel S, Maasjosthusmann U: Determination of metalloproteinases, plasminogen-activators and their inhibitors in the synovial fluids of patients with rheumatoid arthritis during chemical synoviorthesis. Clin Chim Acta. 1996, 244: 17-33.PubMedCrossRef
32.
Koolwijk P, Miltenburg AMM, Van Erck MGM: Activated gelatinase-B (MMP-9) and urokinase-type plasminogen activator in synovial fluids of patients with arthritis. Correlation with clinical and experimental variables of inflammation. J Rheumatol . 1995, 22: 385-393.PubMed
33.
Ogata Y, Enghild JJ, Nagase H: Matrix metalloproteinase 3 (stromelysin) activates the precursor for the human matrix metalloproteinase 9. J Biol Chem. 1992, 267: 3581-3584.PubMed
34.
Wilhelm SM, Collier IE, Marmer BL: SV40-transformed human lung fibroblasts secrete a 92-kDa type IV collagenase which is identical to that secreted by normal human macrophages. J Biol Chem. 1989, 264: 17213-17221.PubMed
35.
Di Girolamo N, Tedla N, Lloyd A, Wakefield D: Expression of matrix metalloproteinases by human plasma cells and B lymphocytes. Eur J Immunol. 1998, 28: 1773-1784. 10.1002/(SICI)1521-4141(199806)28:06<1773::AID-IMMU1773>3.3.CO;2-2.PubMedCrossRef
36.
Vu TH, Shipley JM, Bergers G: MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes. Cell. 1998, 93: 411-422.PubMedPubMedCentralCrossRef
37.
Okada A, Tomasetto C, Lutz Y: Expression of matrix metalloproteinases during rat skin wound healing: evidence that membrane type-1 matrix metalloproteinase is a stromal activator of pro-gelatinase A. J Cell Biol. 1997, 137: 67-77.PubMedPubMedCentralCrossRef
38.
39.
Brown PD, Kleiner DE, Unsworth EJ, Stetler-Stevenson WG: Cellular activation of the 72 kDa type IV procollagenase/TIMP-2 complex. Kidney Int. 1993, 43: 163-170.PubMedCrossRef
40.
Kolkenbrock H, Orgel D, Hecker-Kia A, Noack W, Ulbrich N: The complex between a tissue inhibitor of metalloproteinases (TIMP-2) and 72-kDa progelatinase is a metalloproteinase inhibitor. Eur J Biochem. 1991, 198: 775-781.PubMedCrossRef
41.
Zucker S, Drews M, Conner C: Tissue inhibitor of metalloproteinase-2 (TIMP-2) binds to the catalytic domain of the cell surface receptor, membrane type 1-matrix metalloproteinase 1 (MT1-MMP). J Biol Chem. 1998, 273: 1216-1222.PubMedCrossRef
42.
Sato H, Seiki M: Membrane-type matrix metalloproteinases (MT-MMPs) in tumor metastasis. J Biochem (Tokyo). 1996, 119: 209-215.CrossRef
43.
Yu AE, Hewitt RE, Kleiner DE, Stetler-Stevenson WG: Molecular regulation of cellular invasion--role of gelatinase A and TIMP-2. Biochem Cell Biol. 1996, 74: 823-831.PubMedCrossRef
44.
Brooks PC, Stromblad S, Sanders LC: Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3. Cell. 1996, 85: 683-693.PubMedCrossRef
45.
Pap T, Pap G, Hummel KM: Membrane-type-1 matrix metalloproteinase is abundantly expressed in fibroblasts and osteoclasts at the bone-implant interface of aseptically loosened joint arthroplasties in situ. J Rheumatol. 1999, 26: 166-169.PubMed
46.
Takagi M, Santavirta S, Ida H: The membrane-type-matrix metal-loproteinase/matrix metalloproteinase-2/tissue inhibitor of metallo-proteinase-2 system in periprosthetic connective-tissue remodeling in loose total-hip prostheses. Lab Invest. 1998, 78: 735-742.PubMed
47.
Nawrocki B, Polette M, Burlet H, Birembaut P, Adnet JJ: Expression of gelatinase A and its activator MT1-MMP in the inflammatory periprosthetic response to polyethylene. J Bone Miner Res. 1999, 14: 288-294.PubMedCrossRef
48.
Zvaifler NJ, Firestein GS: Pannus and pannocytes. Alternative models of joint destruction in rheumatoid arthritis. Arthritis Rheum. 1994, 37: 783-789.PubMedCrossRef
49.
Sharp JT, Wolfe F, Mitchell DM, Bloch DA: The progression of erosion and joint space narrowing scores in rheumatoid arthritis during the first twenty-five years of disease. Arthritis Rheum. 1991, 34: 660-668.PubMedCrossRef
50.
Keyszer G, Lambiri I, Nagel R: Circulating levels of matrix metalloproteinases MMP-3 and MMP-1, tissue inhibitor of metalloproteinases 1 (TIMP-1), and MMP-1/TIMP-1 complex in rheumatic disease. Correlation with clinical activity of rheumatoid arthritis versus other surrogate markers. J Rheumatol. 1999, 26: 251-258.PubMed
51.
Zucker S, Lysik RM, Zarrabi MH, Moll U: M(r) 92,000 type IV collagenase is increased in plasma of patients with colon cancer and breast cancer. Cancer Res. 1993, 53: 140-146.PubMed
52.
Nielsen BS, Timshel S, Kjeldsen L: 92kDa type IV collagenase (MMP-9) is expressed in neutrophils and macrophages but not in malignant epithelial cells in human colon cancer. Int J Cancer. 1996, 65: 57-62. 10.1002/(SICI)1097-0215(19960103)65:1<57::AID-IJC10>3.0.CO;2-F.PubMedCrossRef
53.
Sawicki G, Salas E, Murat J, Miszta-Lane H, Radomski MW: Release of gelatinase A during platelet activation mediates aggregation. Nature. 1997, 386: 616-619.PubMedCrossRef
Metadata
Title
Active synovial matrix metalloproteinase-2 is associated with radiographic erosions in patients with early synovitis
Authors
Raphaela Goldbach-Mansky
Jennifer M Lee
Joseph M Hoxworth
David Smith II
Paul Duray
H Ralph Schumacher Jr
Cheryl H Yarboro
John Klippel
David Kleiner
Hani S El-Gabalawy
Publication date
01-02-2000
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 2/2000
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar79

Other articles of this Issue 2/2000

Arthritis Research & Therapy 2/2000 Go to the issue

Review

Death, autoantigen modifications, and tolerance

Commentary

A new model for rheumatoid arthritis?

Review

Risk for rheumatic disease in relation to ethnicity and admixture

Review

B cells in rheumatoid arthritis

Commentary

What can we do about osteoarthritis?

Research article

Acute-phase serum amyloid A production by rheumatoid arthritis synovial tissue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits