The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Trypsin-2 Degrades Human Type II Collagen and Is Expressed and Activated in Mesenchymally Transformed Rheumatoid Arthritis Synovitis Tissue
Open accessAbstract
It has traditionally been believed that only the human collagenases (matrix metalloproteinase-1, -8, and -13) are capable of initiating the degradation of collagens. Here, we show that human trypsin-2 is also capable of cleaving the triple helix of human cartilage collagen type II. We purified human trypsin-2 and tumor-associated trypsin inhibitor by affinity chromatography whereas collagen type II was purified from cartilage extracts using pepsin digestion and salt precipitation. Degradation of type II collagen and gelatin by trypsin-2 was demonstrated with sodium dodecyl sulfate-polyacrylamide gel electrophoresis, zymography, and mass spectrometry, and tumor-associated trypsin inhibitor specifically inhibited this degradation. Although human trypsin-2 efficiently digested type II collagen, bovine trypsin did not. Furthermore, immunohistochemical staining detected trypsin-2 in the fibroblast-like synovial lining and in stromal cells of human rheumatoid arthritis synovial membrane. These findings were confirmed by reverse transcriptase-polymerase chain reaction and nucleotide sequencing. Trypsin-2 alone and complexed with alpha(1)-proteinase inhibitor were also detected in the synovial fluid of affected joints by time-resolved immunofluorometric assay, suggesting that trypsin-2 is activated locally. These results are the first to assess the ability of human trypsin to cleave human type II collagen. Thus, trypsin-2 and its regulators should be further studied for use as markers of prognosis and disease activity in rheumatoid arthritis.
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“The former encodes trypsin 2, involved in type I and II collagen degradation 27,28”
From Sex-specific gene expression signatures of calcific aortic valve stenosis in a large collection of human tissues (2026) · cites this paper as [28]
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Arnett, F. C., Edworthy, S. M., Bloch, D. A., McShane, D. J., Fries, J. F., Cooper, N. S., Healey, L. A., Kaplan, S. R., Liang, M. H., Luthra, H. S., et al. (1988) · Arthritis & Rheumatism · doi:10.1002/art.1780310302 · Cited by 19,753
Cordell, J. L., Falini, B., Erber, W. N., Ghosh, A. K., Abdulaziz, Z., MacDonald, S. M., Pulford, K. A. F., Stein, H., & Mason, D. Y. (1984) · Journal of Histochemistry & Cytochemistry · doi:10.1177/32.2.6198355 · Cited by 3,147
Biochemical Characterization of Human Collagenase-3
Knäuper, V., López-Otı́n, C., Smith, B., Knight, G. C., & Murphy, G. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.3.1544 · Cited by 882
[2] Preparation and characterization of the different types of collagen
Miller, E. J., & Rhodes, R. K. (1982) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(82)82059-4 · Cited by 753
Tumor targeting with a selective gelatinase inhibitor
Koivunen, E., Arap, W., Valtanen, H., Rainisalo, A., Medina, O. P., Heikkilä, P., Kantor, C., Gahmberg, C. G., Salo, T. A., Konttinen, Y. T., et al. (1999) · Nature Biotechnology · doi:10.1038/11703 · Cited by 567
Self-citationMatrix Metalloproteinase-8 Is Expressed in Rheumatoid Synovial Fibroblasts and Endothelial Cells
Hanemaaijer, R., Sorsa, T. A., Konttinen, Y. T., Ding, Y., Sutinen, M., Visser, H., van Hinsbergh, V. W. M., Helaakoski, T., Kainulainen, T., Rönkä, H., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.50.31504 · Cited by 489
Self-citationRedesigning Trypsin: Alteration of Substrate Specificity
Craik, C. S., Largman, C., Fletcher, T. S., Roczniak, S. O., Barr, P. J., Fletterick, R. J., & Rutter, W. J. (1985) · Science · doi:10.1126/science.3838593 · Cited by 364
Activation of Type IV Procollagenases by Human Tumor-associated Trypsin-2
Sorsa, T. A., Salo, T. A., Koivunen, E., Tyynelä, J., Konttinen, Y. T., Bergmann, U., Tuuttila, A., Niemi, E., Teronen, O. P., Heikkilä, P., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.34.21067 · Cited by 215
Self-citationHistomorphological Basis of Articular Cartilage Destruction in Rheumatoid Arthritis
Fassbender, H. G. (1983) · Collagen and Related Research · doi:10.1016/s0174-173x(83)80040-5 · Cited by 195
Evanson, J. M., Jeffrey, J. J., & Krane, S. M. (1967) · Science · doi:10.1126/science.158.3800.499 · Cited by 195
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Research works printed but not linked: 1
- Fassbender, 1973, Morphologisches substrat und pathogenese der rheumatischen erkrankungen, Therapiewoche, 23, 611
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Houessou, U., Zamani, P., Manikpurage, H. D., Li, Z., Gaudreault, N., Dahmene, M., Dagenais, F., Couture, C., Clavel, M.-A., Pibarot, P., et al. (2026) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2026.120791 · Cited by 1
Metadata
- Authors
- Stenman, M., Ainola, M., Valmu, L., Bjartell, A., Ma, G., Stenman, U.-H., Sorsa, T., Luukkainen, R., & Konttinen, Y. T.
- Affiliations
- University of Helsinki (FI)
- Tekonivelsairaala Orton (FI)
- Helsinki University Hospital (FI)
- Corresponding author
- Stenman, Ulf-Håkan
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2005-10
- Volume
- 167
- Issue
- 4
- Pages
- 1119-1124
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC1603685
- OpenAlex
- W2092049566
- Cited by
- 37
- References
- 29
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 1 · 2014: 4 · 2013: 3
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Ministry of Education
- Sigrid Juséliuksen Säätiö
- Helsingin Yliopisto
- K. Albin Johanssons Stiftelse
- Helsingin ja Uudenmaan Sairaanhoitopiiri (TI020 Y0002, TYH3306, TYH5306)
- Academy of Finland
- Finska Läkaresällskapet
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Keywords
- type II collagen, collagen degradation, rheumatoid arthritis, synovium, tumor-associated trypsin inhibitor, alpha-1-antitrypsin, mesenchymal transition, synovial fluid, cartilage collagen, gelatin, matrix metalloproteinases, disease markers
- MeSH terms
- Adult, Aged, Aged, 80 and over, Amino Acid Sequence, Animals, Antibodies, Monoclonal, Arthritis, Rheumatoid, Base Sequence, Cattle, Cells, Cultured, Electrophoresis, Polyacrylamide Gel, Europium, Female, Fluorometry, Humans, Immunohistochemistry, Male, Middle Aged, Molecular Sequence Data, Molecular Weight, RNA, Messenger, Mass Spectrometry, Synovial Fluid, Synovial Membrane, Trypsin, Trypsin Inhibitor, Kazal Pancreatic, Trypsinogen, Cell Culture Techniques, Reverse Transcriptase Polymerase Chain Reaction, Matrix Metalloproteinase 8, Collagen Type II
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