Ann Rheum Dis

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS REGISTER


[Advanced]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this link to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Add article to my folders
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yoshihara, Y.
Right arrow Articles by Okada, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yoshihara, Y.
Right arrow Articles by Okada, Y.
Ann Rheum Dis 2000;59:455-461 ( June )

Extended report

Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids from patients with rheumatoid arthritis or osteoarthritis Yasuo Yoshiharaa, Hiroyuki Nakamurab, Ken'ichi Obatac, Harumoto Yamadad, Taro Hayakawae, Kyosuke Fujikawaa, Yasunori Okadab

a Department of Orthopaedic Surgery, National Defence Medical College, b Department of Pathology, School of Medicine, Keio University, c Biopharmaceutical Department, Fuji Chemical Industries Ltd, d Department of Orthopaedic Surgery, Fujita Health University, Second Hospital, e Department of Biochemistry, School of Dentistry, Aichi-Gakuin University

Correspondence to: Dr Yasunori Okada, Department of Pathology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-0016, Japan Email: okada{at}med.keio.ac.jp

Accepted for publication 10 January 2000

OBJECTIVE---Matrix metalloproteinases (MMPs) are expressed in joint tissues of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). The objective of this study was to define the steady state levels of seven different MMPs and two tissue inhibitors of metalloproteinases (TIMPs) as well as the potential metalloproteinase activity in the synovial fluid (SF) to provide more insight into the role of MMPs in cartilage destruction in RA and OA.
METHODS---Levels of MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-13, TIMP-1, and TIMP-2 in SF aspirated from knee joints of 97 patients with RA and 103 patients with OA were measured by the corresponding one step sandwich enzyme immunoassays. Proteolytic activity of MMPs in these SFs was examined in an assay using [3H]carboxymethylated transferrin substrate in the presence of inhibitors of serine and cysteine proteinases after activation with p-aminophenylmercuric acetate (APMA). Destruction of RA knee joints was radiographically evaluated.
RESULTS---Levels of MMP-1, MMP-2, MMP-3, MMP-8, and MMP-9 were significantly higher in RA SF than in OA SF. MMP-7 and MMP-13 were detectable in more than 45% of RA SFs and in less than 20% of OA SFs, respectively. Among the MMPs examined, MMP-3 levels were extremely high compared with those of other MMPs. Direct correlations were seen between the levels of MMP-1 and MMP-3 and between those of MMP-8 and MMP-9 in RA SF. Although the levels of MMP-1 and MMP-3 increased even in the early stage of RA, those of MMP-8 and MMP-9 were low in the early stage and increased with the progression of RA. Molar ratios of the total amounts of the MMPs to those of the TIMPs were 5.2-fold higher in patients with RA than in OA, which was significant. APMA-activated metalloproteinase activity in SF showed a similar result, and a direct correlation was seen between the molar ratios and the activity in RA SF.
CONCLUSIONS---Our results show that high levels of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, and TIMP-1 are present in RA SF and suggest that once these MMPs are fully activated, they have an imbalance against TIMPs, which may contribute to the cartilage destruction in RA.

© 2000 by Annals of the Rheumatic Diseases


This article has been cited by other articles:


Home page
 Ann Rheum DisHome page
I Tchetverikov, M C Kraan, B van El, R Hanemaaijer, J DeGroot, and T W J Huizinga
Leflunomide and methotrexate reduce levels of activated matrix metalloproteinases in complexes with {alpha}2 macroglobulin in serum of rheumatoid arthritis patients
Ann Rheum Dis, January 1, 2008; 67(1): 128 - 130.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
Y.-C. Chiu, R.-S. Yang, K.-H. Hsieh, Y.-C. Fong, T.-D. Way, T.-S. Lee, H.-C. Wu, W.-M. Fu, and C.-H. Tang
Stromal Cell-Derived Factor-1 Induces Matrix Metalloprotease-13 Expression in Human Chondrocytes
Mol. Pharmacol., September 1, 2007; 72(3): 695 - 703.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
S. Sandya and P. R. Sudhakaran
Effect of Glycosaminoglycans on Matrix Metalloproteinases in Type II Collagen-Induced Experimental Arthritis
Experimental Biology and Medicine, May 1, 2007; 232(5): 629 - 637.
[Abstract] [Full Text] [PDF]

Home page
 Rheumatology (Oxford)Home page
N. Amos, S. Lauder, A. Evans, M. Feldmann, and J. Bondeson
Adenoviral gene transfer into osteoarthritis synovial cells using the endogenous inhibitor I{kappa}B{alpha} reveals that most, but not all, inflammatory and destructive mediators are NF{kappa}B dependent
Rheumatology, October 1, 2006; 45(10): 1201 - 1209.
[Abstract] [Full Text] [PDF]

Home page
 Rheumatology (Oxford)Home page
T. Hiramitsu, T. Yasuda, H. Ito, M. Shimizu, S. M. Julovi, T. Kakinuma, M. Akiyoshi, M. Yoshida, and T. Nakamura
Intercellular adhesion molecule-1 mediates the inhibitory effects of hyaluronan on interleukin-1{beta}-induced matrix metalloproteinase production in rheumatoid synovial fibroblasts via down-regulation of NF-{kappa}B and p38
Rheumatology, July 1, 2006; 45(7): 824 - 832.
[Abstract] [Full Text] [PDF]

Home page
 Ann Rheum DisHome page
N J Peake, H E Foster, K Khawaja, T E Cawston, and A D Rowan
Assessment of the clinical significance of gelatinase activity in patients with juvenile idiopathic arthritis using quantitative protein substrate zymography
Ann Rheum Dis, April 1, 2006; 65(4): 501 - 507.
[Abstract] [Full Text] [PDF]

Home page
 Rheumatology (Oxford)Home page
C.-H. Chen, K.-C. Lin, D. T. Y. Yu, C. Yang, F. Huang, H.-A. Chen, T.-H. Liang, H.-T. Liao, C.-Y. Tsai, J. C. C. Wei, et al.
Serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in ankylosing spondylitis: MMP-3 is a reproducibly sensitive and specific biomarker of disease activity
Rheumatology, April 1, 2006; 45(4): 414 - 420.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Grau, P. J. Richards, B. Kerr, C. Hughes, B. Caterson, A. S. Williams, U. Junker, S. A. Jones, T. Clausen, and M. Ehrmann
The Role of Human HtrA1 in Arthritic Disease
J. Biol. Chem., March 10, 2006; 281(10): 6124 - 6129.
[Abstract] [Full Text] [PDF]

Home page
 Ann Rheum DisHome page
T G Morgan, A D Rowan, S C Dickinson, D Jones, A P Hollander, D Deehan, and T E Cawston
Human nasal cartilage responds to oncostatin M in combination with interleukin 1 or tumour necrosis factor {alpha} by the release of collagen fragments via collagenases
Ann Rheum Dis, February 1, 2006; 65(2): 184 - 190.
[Abstract] [Full Text] [PDF]

Home page
 Rheumatology (Oxford)Home page
N. J. Peake, K. Khawaja, A. Myers, D. Jones, T. E. Cawston, A. D. Rowan, and H. E. Foster
Levels of matrix metalloproteinase (MMP)-1 in paired sera and synovial fluids of juvenile idiopathic arthritis patients: relationship to inflammatory activity, MMP-3 and tissue inhibitor of metalloproteinases-1 in a longitudinal study
Rheumatology, November 1, 2005; 44(11): 1383 - 1389.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
H. Yoshifuji, H. Umehara, H. Maruyama, M. Itoh, M. Tanaka, D. Kawabata, T. Fujii, and T. Mimori
Amelioration of experimental arthritis by a calpain-inhibitory compound: regulation of cytokine production by E-64-d in vivo and in vitro
Int. Immunol., October 1, 2005; 17(10): 1327 - 1336.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. A. Pattoli, J. F. MacMaster, K. R. Gregor, and J. R. Burke
Collagen and Aggrecan Degradation Is Blocked in Interleukin-1-Treated Cartilage Explants by an Inhibitor of I{kappa}B Kinase through Suppression of Metalloproteinase Expression
J. Pharmacol. Exp. Ther., October 1, 2005; 315(1): 382 - 388.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
F. W.S. Ko, C. Diba, M. Roth, K. McKay, P. R.A. Johnson, C. Salome, and G. G. King
A Comparison of Airway and Serum Matrix Metalloproteinase-9 Activity Among Normal Subjects, Asthmatic Patients, and Patients With Asthmatic Mucus Hypersecretion
Chest, June 1, 2005; 127(6): 1919 - 1927.
[Abstract] [Full Text] [PDF]

Home page
 Ann Rheum DisHome page
I Tchetverikov, L S Lohmander, N Verzijl, T W J Huizinga, J M TeKoppele, R Hanemaaijer, and J DeGroot
MMP protein and activity levels in synovial fluid from patients with joint injury, inflammatory arthritis, and osteoarthritis
Ann Rheum Dis, May 1, 2005; 64(5): 694 - 698.
[Abstract] [Full Text] [PDF]

Home page
 Protein Eng Des SelHome page
S. Vessillier, G. Adams, and Y. Chernajovsky
Latent cytokines: development of novel cleavage sites and kinetic analysis of their differential sensitivity to MMP-1 and MMP-3
Protein Eng. Des. Sel., December 1, 2004; 17(12): 829 - 835.
[Abstract] [Full Text] [PDF]

Home page
 Ann Rheum DisHome page
V Bjerkeli, B Halvorsen, J K Damas, I Nordoy, A Yndestad, P Aukrust, and S S Froland
Expression of matrix metalloproteinases in patients with Wegener's granulomatosis
Ann Rheum Dis, December 1, 2004; 63(12): 1659 - 1663.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. Ray, D. Kumar, A. Shakya, C. R. Brown, J. L. Cook, and B. K. Ray
Serum Amyloid A-Activating Factor-1 (SAF-1) Transgenic Mice Are Prone to Develop a Severe Form of Inflammation-Induced Arthritis
J. Immunol., October 1, 2004; 173(7): 4684 - 4691.
[Abstract] [Full Text] [PDF]

Home page
 Ann Rheum DisHome page
I Tchetverikov, H K Ronday, B van El, G H Kiers, N Verzijl, J M TeKoppele, T W J Huizinga, J DeGroot, and R Hanemaaijer
MMP profile in paired serum and synovial fluid samples of patients with rheumatoid arthritis
Ann Rheum Dis, July 1, 2004; 63(7): 881 - 883.
[Abstract] [Full Text] [PDF]

Home page
 Ann Rheum DisHome page
K Joronen, R Ala-aho, M-L Majuri, H Alenius, V-M Kahari, and E Vuorio
Adenovirus mediated intra-articular expression of collagenase-3 (MMP-13) induces inflammatory arthritis in mice
Ann Rheum Dis, June 1, 2004; 63(6): 656 - 664.
[Abstract] [Full Text]

Home page
 J. Immunol.Home page
J. H. M. van Bilsen, J. P. A. Wagenaar-Hilbers, M. C. J. T. Grosfeld-Stulemeijer, M. J. F. van der Cammen, M. E. A. van Dijk, W. van Eden, and M. H. M. Wauben
Matrix Metalloproteinases as Targets for the Immune System during Experimental Arthritis
J. Immunol., April 15, 2004; 172(8): 5063 - 5068.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
A. Matsuyama, N. Sakai, M. Ishigami, H. Hiraoka, S. Kashine, A. Hirata, T. Nakamura, S. Yamashita, and Y. Matsuzawa
Matrix Metalloproteinases as Novel Disease Markers in Takayasu Arteritis
Circulation, September 23, 2003; 108(12): 1469 - 1473.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
A. D. Rowan, W. Hui, T. E. Cawston, and C. D. Richards
Adenoviral Gene Transfer of Interleukin-1 in Combination with Oncostatin M Induces Significant Joint Damage in a Murine Model
Am. J. Pathol., June 1, 2003; 162(6): 1975 - 1984.
[Abstract] [Full Text] [PDF]

Home page
 Rheumatology (Oxford)Home page
S. S. Shin, M. Jin, H. J. Jung, B. Kim, H. Jeon, J. J. Choi, J. M. Kim, B. W. Cho, S. H. Chung, Y. W. Lee, et al.
Suppressive effects of PG201, an ethanol extract from herbs, on collagen-induced arthritis in mice
Rheumatology, May 1, 2003; 42(5): 665 - 672.
[Abstract] [Full Text] [PDF]

Home page
 Ann Rheum DisHome page
H Tsuboi, Y Matsui, K Hayashida, S Yamane, M Maeda-Tanimura, A Nampei, J Hashimoto, R Suzuki, H Yoshikawa, and T Ochi
Tartrate resistant acid phosphatase (TRAP) positive cells in rheumatoid synovium may induce the destruction of articular cartilage
Ann Rheum Dis, March 1, 2003; 62(3): 196 - 203.
[Abstract] [Full Text] [PDF]

Home page
 Ann Rheum DisHome page
W Hui, T Cawston, and A D Rowan
Transforming growth factor {beta}1 and insulin-like growth factor 1 block collagen degradation induced by oncostatin M in combination with tumour necrosis factor {alpha} from bovine cartilage
Ann Rheum Dis, February 1, 2003; 62(2): 172 - 174.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
E. C. Tsark, W. Wang, Y.-C. Teng, D. Arkfeld, G. R. Dodge, and S. Kovats
Differential MHC Class II-Mediated Presentation of Rheumatoid Arthritis Autoantigens by Human Dendritic Cells and Macrophages
J. Immunol., December 1, 2002; 169(11): 6625 - 6633.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
T. Itoh, H. Matsuda, M. Tanioka, K. Kuwabara, S. Itohara, and R. Suzuki
The Role of Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 in Antibody-Induced Arthritis
J. Immunol., September 1, 2002; 169(5): 2643 - 2647.
[Abstract] [Full Text] [PDF]

Home page
 Rheumatology (Oxford)Home page
P. A. Klimiuk, S. Sierakowski, R. Latosiewicz, B. Cylwik, J. Skowronski, and J. Chwiecko
Serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in different histological variants of rheumatoid synovitis
Rheumatology, January 1, 2002; 41(1): 78 - 87.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
N. S. Patil, A. Pashine, M. P. Belmares, W. Liu, B. Kaneshiro, J. Rabinowitz, H. McConnell, and E. D. Mellins
Rheumatoid Arthritis (RA)-Associated HLA-DR Alleles Form Less Stable Complexes with Class II-Associated Invariant Chain Peptide Than Non-RA-Associated HLA-DR Alleles
J. Immunol., December 15, 2001; 167(12): 7157 - 7168.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
W. W. Noll, D. R. Belloni, J. L. Rutter, C. A. Storm, A. R. Schned, L. Titus-Ernstoff, M. S. Ernstoff, and C. E. Brinckerhoff
Loss of Heterozygosity on Chromosome 11q22-23 in Melanoma Is Associated with Retention of the Insertion Polymorphism in the Matrix Metalloproteinase-1 Promoter
Am. J. Pathol., February 1, 2001; 158(2): 691 - 697.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS REGISTER
Terms and conditions relating to subscriptions purchased online  ¦  Website terms and conditions  ¦  Privacy policy
Copyright © 2000 BMJ Publishing Group Ltd & European League Against Rheumatism