Expression and tissue localization of membrane-types 1, 2, and 3 matrix metalloproteinases in rheumatoid synovium

Hajime Yamanaka, Ken Ichi Makino, Masayuki Takizawa, Hiroyuki Nakamura, Noboru Fujimoto, Hideshige Moriya, Ryoichi Nemori, Hiroshi Sato, Motoharu Seiki, Yasunori Okada

Research output: Contribution to journalArticle

62 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)677-687
Number of pages11
JournalLaboratory Investigation
Volume80
Issue number5
Publication statusPublished - 2000 May

Fingerprint

Matrix Metalloproteinase 16
Matrix Metalloproteinase 15
Matrix Metalloproteinase 14
Synovial Membrane
Matrix Metalloproteinases
Rheumatoid Arthritis
Membrane-Associated Matrix Metalloproteinases
Tissue Inhibitor of Metalloproteinase-2
Enzyme Precursors
Matrix Metalloproteinase Inhibitors
Gelatin
progelatinase
Immunoenzyme Techniques
Cartilage
In Situ Hybridization
Joints
Immunohistochemistry
Polymerase Chain Reaction
Messenger RNA

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Yamanaka, H., Makino, K. I., Takizawa, M., Nakamura, H., Fujimoto, N., Moriya, H., ... Okada, Y. (2000). Expression and tissue localization of membrane-types 1, 2, and 3 matrix metalloproteinases in rheumatoid synovium. Laboratory Investigation, 80(5), 677-687.

Expression and tissue localization of membrane-types 1, 2, and 3 matrix metalloproteinases in rheumatoid synovium. / Yamanaka, Hajime; Makino, Ken Ichi; Takizawa, Masayuki; Nakamura, Hiroyuki; Fujimoto, Noboru; Moriya, Hideshige; Nemori, Ryoichi; Sato, Hiroshi; Seiki, Motoharu; Okada, Yasunori.

In: Laboratory Investigation, Vol. 80, No. 5, 05.2000, p. 677-687.

Research output: Contribution to journalArticle

Yamanaka, H, Makino, KI, Takizawa, M, Nakamura, H, Fujimoto, N, Moriya, H, Nemori, R, Sato, H, Seiki, M & Okada, Y 2000, 'Expression and tissue localization of membrane-types 1, 2, and 3 matrix metalloproteinases in rheumatoid synovium', Laboratory Investigation, vol. 80, no. 5, pp. 677-687.
Yamanaka H, Makino KI, Takizawa M, Nakamura H, Fujimoto N, Moriya H et al. Expression and tissue localization of membrane-types 1, 2, and 3 matrix metalloproteinases in rheumatoid synovium. Laboratory Investigation. 2000 May;80(5):677-687.
Yamanaka, Hajime ; Makino, Ken Ichi ; Takizawa, Masayuki ; Nakamura, Hiroyuki ; Fujimoto, Noboru ; Moriya, Hideshige ; Nemori, Ryoichi ; Sato, Hiroshi ; Seiki, Motoharu ; Okada, Yasunori. / Expression and tissue localization of membrane-types 1, 2, and 3 matrix metalloproteinases in rheumatoid synovium. In: Laboratory Investigation. 2000 ; Vol. 80, No. 5. pp. 677-687.
@article{eabb01d640ed404e997939d78498e254,
title = "Expression and tissue localization of membrane-types 1, 2, and 3 matrix metalloproteinases in rheumatoid synovium",
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.",
author = "Hajime Yamanaka and Makino, {Ken Ichi} and Masayuki Takizawa and Hiroyuki Nakamura and Noboru Fujimoto and Hideshige Moriya and Ryoichi Nemori and Hiroshi Sato and Motoharu Seiki and Yasunori Okada",
year = "2000",
month = "5",
language = "English",
volume = "80",
pages = "677--687",
journal = "Laboratory investigation; a journal of technical methods and pathology",
issn = "0023-6837",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Expression and tissue localization of membrane-types 1, 2, and 3 matrix metalloproteinases in rheumatoid synovium

AU - Yamanaka, Hajime

AU - Makino, Ken Ichi

AU - Takizawa, Masayuki

AU - Nakamura, Hiroyuki

AU - Fujimoto, Noboru

AU - Moriya, Hideshige

AU - Nemori, Ryoichi

AU - Sato, Hiroshi

AU - Seiki, Motoharu

AU - Okada, Yasunori

PY - 2000/5

Y1 - 2000/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0034076456&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034076456&partnerID=8YFLogxK

M3 - Article

C2 - 10830778

AN - SCOPUS:0034076456

VL - 80

SP - 677

EP - 687

JO - Laboratory investigation; a journal of technical methods and pathology

JF - Laboratory investigation; a journal of technical methods and pathology

SN - 0023-6837

IS - 5

ER -