Expression and tissue localization of membrane-types 1, 2, and 3 matrix metalloproteinases in rheumatoid synovium - PubMed (original) (raw)
Expression and tissue localization of membrane-types 1, 2, and 3 matrix metalloproteinases in rheumatoid synovium
H Yamanaka et al. Lab Invest. 2000 May.
Free article
Abstract
In vitro, membrane-type matrix metalloproteinases (MT-MMP) are known to activate the zymogen of MMP-2 (proMMP-2, progelatinase A), which is one of the key MMP in joint destruction in rheumatoid arthritis. In the present study, we examined the production and activation of proMMP-2, and the expression of MT1-MMP, MT2-MMP, and MT3-MMP, their correlation with proMMP-2 activation, and their localization in rheumatoid synovial tissue. Using sandwich enzyme immunoassay and gelatin zymography techniques, proMMP-2 production levels and activation ratios were found to be significantly higher in rheumatoid synovium compared with normal synovium (p < 0.01). Quantitative RT-PCR analyses demonstrated that MT1-MMP and MT3-MMP were expressed in all rheumatoid synovial tissue (30 of 30 cases), but that the mean expression level of MT1-MMP was approximately 11-fold higher than MT3-MMP. Significant correlation was found between the mRNA expression level of MT1-MMP and the activation ratio of proMMP-2 (p < 0.01). In situ hybridization indicated that the hyperplastic lining cells of rheumatoid synovium expressed MT1-MMP. Immunohistochemistry demonstrated that MT1-MMP was co-localized with MMP-2 and with a tissue inhibitor of metalloproteinase-2, and was mainly located in the rheumatoid synovial lining cells. In situ zymography of rheumatoid synovium showed gelatinolytic activity, predominantly in the lining cell layer. This activity was blocked when incubated with BB94, a specific MMP inhibitor. These results demonstrate that MT1-MMP plays an important role in the activation of proMMP-2 in the rheumatoid synovial lining cell layer, and suggest that its activity may be involved in the cartilage destruction of rheumatoid arthritis.
Similar articles
- Enhanced production and activation of progelatinase A mediated by membrane-type 1 matrix metalloproteinase in human papillary thyroid carcinomas.
Nakamura H, Ueno H, Yamashita K, Shimada T, Yamamoto E, Noguchi M, Fujimoto N, Sato H, Seiki M, Okada Y. Nakamura H, et al. Cancer Res. 1999 Jan 15;59(2):467-73. Cancer Res. 1999. PMID: 9927064 - Enhanced production and activation of progelatinase A mediated by membrane-type 1 matrix metalloproteinase in human oral squamous cell carcinomas: implications for lymph node metastasis.
Shimada T, Nakamura H, Yamashita K, Kawata R, Murakami Y, Fujimoto N, Sato H, Seiki M, Okada Y. Shimada T, et al. Clin Exp Metastasis. 2000;18(2):179-88. doi: 10.1023/a:1006749501682. Clin Exp Metastasis. 2000. PMID: 11235994 - Differential expression pattern of membrane-type matrix metalloproteinases in rheumatoid arthritis.
Pap T, Shigeyama Y, Kuchen S, Fernihough JK, Simmen B, Gay RE, Billingham M, Gay S. Pap T, et al. Arthritis Rheum. 2000 Jun;43(6):1226-32. doi: 10.1002/1529-0131(200006)43:6<1226::AID-ANR5>3.0.CO;2-4. Arthritis Rheum. 2000. PMID: 10857781 - Membrane-type matrix metalloproteinases (MT-MMPs) in cell invasion.
Sato H, Okada Y, Seiki M. Sato H, et al. Thromb Haemost. 1997 Jul;78(1):497-500. Thromb Haemost. 1997. PMID: 9198203 Review. - Cell surface activation of progelatinase A (proMMP-2) and cell migration.
Nagase H. Nagase H. Cell Res. 1998 Sep;8(3):179-86. doi: 10.1038/cr.1998.18. Cell Res. 1998. PMID: 9791731 Review.
Cited by
- Impaired regulation of MMP2/16-MLCK3 by miR-146a-5p increased susceptibility to myocardial ischaemic injury in aging mice.
Dong M, Chen D, Zhu Y, Yang S, Kumar S, Zhang R, Zhou Y, Yang Z, Zheng N, Zhu T, Xiang J, Liu Y, Kang L, Liu J. Dong M, et al. Cardiovasc Res. 2023 May 2;119(3):786-801. doi: 10.1093/cvr/cvac104. Cardiovasc Res. 2023. PMID: 35727952 Free PMC article. - Localization, Shedding, Regulation and Function of Aminopeptidase N/CD13 on Fibroblast like Synoviocytes.
Morgan RL, Behbahani-Nejad N, Endres J, Amin MA, Lepore NJ, Du Y, Urquhart A, Chung KC, Fox DA. Morgan RL, et al. PLoS One. 2016 Sep 22;11(9):e0162008. doi: 10.1371/journal.pone.0162008. eCollection 2016. PLoS One. 2016. PMID: 27658265 Free PMC article. - Effect of Laminin-A4 inhibition on cluster formation of human osteoarthritic chondrocytes.
Moazedi-Fuerst FC, Gruber G, Stradner MH, Guidolin D, Jones JC, Bodo K, Wagner K, Peischler D, Krischan V, Weber J, Sadoghi P, Glehr M, Leithner A, Graninger WB. Moazedi-Fuerst FC, et al. J Orthop Res. 2016 Mar;34(3):419-26. doi: 10.1002/jor.23036. Epub 2015 Sep 24. J Orthop Res. 2016. PMID: 26295200 Free PMC article. - The role of interleukin 6 in the pathophysiology of rheumatoid arthritis.
Srirangan S, Choy EH. Srirangan S, et al. Ther Adv Musculoskelet Dis. 2010 Oct;2(5):247-56. doi: 10.1177/1759720X10378372. Ther Adv Musculoskelet Dis. 2010. PMID: 22870451 Free PMC article. - Matrix metalloproteinases, a disintegrin and metalloproteinases, and a disintegrin and metalloproteinases with thrombospondin motifs in non-neoplastic diseases.
Shiomi T, Lemaître V, D'Armiento J, Okada Y. Shiomi T, et al. Pathol Int. 2010 Jul;60(7):477-96. doi: 10.1111/j.1440-1827.2010.02547.x. Pathol Int. 2010. PMID: 20594269 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous