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Differential expression pattern of membrane-type matrix metalloproteinases in rheumatoid arthritis.
Arthritis Rheum. 2000 Jun; 43(6):1226-32.AR

Abstract

OBJECTIVE

To study the expression of messenger RNA (mRNA) for different membrane-type matrix metalloproteinases (MT-MMPs) and compare their expression pattern in rheumatoid arthritis (RA) and normal synovium.

METHODS

Polymerase chain reaction (PCR) with specific primers was performed to analyze the presence of MT1-, MT2-, MT3-, and MT4-MMP in synovial tissue and synovial fibroblasts from 10 patients with RA and 4 subjects without arthritis. In addition, in situ hybridization with digoxigenin-labeled RNA probes was used to investigate the expression pattern of MT-MMPs in the synovium of these subjects. MT-MMP-expressing cells were characterized by immunohistochemical double labeling with anti-CD68 monoclonal antibodies.

RESULTS

Reverse transcription-PCR revealed the expression of MT1-, MT2-, MT3-, and MT4-MMP mRNA in all tissues and cell cultures examined. However, in situ hybridization showed considerable differences in the expression pattern of the different MT-MMPs in RA synovium. MT1- and MT3-MMP mRNA were highly expressed in both the lining and the sublining layer, with more intense staining in the lining. Immunohistochemical double labeling demonstrated the presence of mRNA for MT1-MMP in fibroblasts and macrophages, as well as in osteoclast-like cells at sites of bone resorption. Expression of MT3-MMP mRNA was seen in fibroblasts and some macrophages. Expression of MT2- and MT4-MMP was characterized by staining of only a few CD68-negative fibroblasts, and no differences could be found between the lining and sublining. Normal synovial samples showed only limited staining for all MT-MMPs.

CONCLUSION

Our results indicate a role for MT1-MMP not only in the matrix degradation by fibroblasts, but also in osteoclast-mediated bone resorption in RA. Given the ability of MT1-MMP to activate MMP-2 and MMP-13, the findings also point to a cooperation between fibroblasts and macrophages in degrading cartilage and bone. While MT3-MMP is also intensely expressed in RA synovium, MT2- and MT4-MMP appear not to be involved in rheumatoid joint destruction.

Authors+Show Affiliations

WHO Collaborating Center for Molecular Biology and Novel Therapeutic Strategies for Rheumatic Diseases, University Hospital, Zurich, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10857781

Citation

Pap, T, et al. "Differential Expression Pattern of Membrane-type Matrix Metalloproteinases in Rheumatoid Arthritis." Arthritis and Rheumatism, vol. 43, no. 6, 2000, pp. 1226-32.
Pap T, Shigeyama Y, Kuchen S, et al. Differential expression pattern of membrane-type matrix metalloproteinases in rheumatoid arthritis. Arthritis Rheum. 2000;43(6):1226-32.
Pap, T., Shigeyama, Y., Kuchen, S., Fernihough, J. K., Simmen, B., Gay, R. E., Billingham, M., & Gay, S. (2000). Differential expression pattern of membrane-type matrix metalloproteinases in rheumatoid arthritis. Arthritis and Rheumatism, 43(6), 1226-32.
Pap T, et al. Differential Expression Pattern of Membrane-type Matrix Metalloproteinases in Rheumatoid Arthritis. Arthritis Rheum. 2000;43(6):1226-32. PubMed PMID: 10857781.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential expression pattern of membrane-type matrix metalloproteinases in rheumatoid arthritis. AU - Pap,T, AU - Shigeyama,Y, AU - Kuchen,S, AU - Fernihough,J K, AU - Simmen,B, AU - Gay,R E, AU - Billingham,M, AU - Gay,S, PY - 2000/6/17/pubmed PY - 2000/7/8/medline PY - 2000/6/17/entrez SP - 1226 EP - 32 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 43 IS - 6 N2 - OBJECTIVE: To study the expression of messenger RNA (mRNA) for different membrane-type matrix metalloproteinases (MT-MMPs) and compare their expression pattern in rheumatoid arthritis (RA) and normal synovium. METHODS: Polymerase chain reaction (PCR) with specific primers was performed to analyze the presence of MT1-, MT2-, MT3-, and MT4-MMP in synovial tissue and synovial fibroblasts from 10 patients with RA and 4 subjects without arthritis. In addition, in situ hybridization with digoxigenin-labeled RNA probes was used to investigate the expression pattern of MT-MMPs in the synovium of these subjects. MT-MMP-expressing cells were characterized by immunohistochemical double labeling with anti-CD68 monoclonal antibodies. RESULTS: Reverse transcription-PCR revealed the expression of MT1-, MT2-, MT3-, and MT4-MMP mRNA in all tissues and cell cultures examined. However, in situ hybridization showed considerable differences in the expression pattern of the different MT-MMPs in RA synovium. MT1- and MT3-MMP mRNA were highly expressed in both the lining and the sublining layer, with more intense staining in the lining. Immunohistochemical double labeling demonstrated the presence of mRNA for MT1-MMP in fibroblasts and macrophages, as well as in osteoclast-like cells at sites of bone resorption. Expression of MT3-MMP mRNA was seen in fibroblasts and some macrophages. Expression of MT2- and MT4-MMP was characterized by staining of only a few CD68-negative fibroblasts, and no differences could be found between the lining and sublining. Normal synovial samples showed only limited staining for all MT-MMPs. CONCLUSION: Our results indicate a role for MT1-MMP not only in the matrix degradation by fibroblasts, but also in osteoclast-mediated bone resorption in RA. Given the ability of MT1-MMP to activate MMP-2 and MMP-13, the findings also point to a cooperation between fibroblasts and macrophages in degrading cartilage and bone. While MT3-MMP is also intensely expressed in RA synovium, MT2- and MT4-MMP appear not to be involved in rheumatoid joint destruction. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/10857781/Differential_expression_pattern_of_membrane_type_matrix_metalloproteinases_in_rheumatoid_arthritis_ L2 - https://doi.org/10.1002/1529-0131(200006)43:6<1226::AID-ANR5>3.0.CO;2-4 DB - PRIME DP - Unbound Medicine ER -