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Temporospatial expression of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in mouse antigen-induced arthritis

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Abstract

Several lines of evidence speak for an important role of matrix metalloproteinases (MMPs) in the development of progressive joint destruction. To better understand the role of MMPs and their tissue inhibitors (TIMPs) in this process, we have used the antigen-induced arthritis model to study the temporospatial expression of several MMPs and TIMPs during the progression of arthritis. Arthritis was induced by a single intra-articular injection of methylated bovine serum albumin (mBSA) into one or both knee joints of adult mice previously immunised against mBSA. Samples were collected at 3, 7, 21 and 42 days after induction of arthritis for histology and RNA extraction, and analysed by Northern hybridisation, histochemistry and immunohistochemistry for production of several MMPs and TIMPs −1, −2 and −3. A systematic analysis of MMP and TIMP mRNA levels in mouse knee joints demonstrated a general upregulation of both MMPs and TIMPs during progression of arthritis. Upregulation of MMP-9, −13 and −14 coincided with the advancement of cartilage degeneration, but the expression patterns of MMP-9 and −13 also followed the course of synovial inflammation. TIMPs were steadily upregulated throughout the examination period. Immunohistochemical localisation of MMPs and TIMPs suggested the synovium to be the major source of MMP and TIMP production in arthritis, although articular cartilage chondrocytes also showed an increased production of both MMPs and TIMPs.

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Acknowledgements

The authors are grateful to Tuula Oivanen, Merja Lakkisto and Maria Ström as well as to the personnel of the animal facilities for expert technical assistance. This study was supported by grants from the Academy of Finland (projects 52940 and 45996), Sigrid Jusèlius Foundation, the Cancer Research Foundation of Finland, Turku University Central Hospital, and by research contract with Finnish Life and Pension Insurance Companies. K.J. is a recipient of a training grant from Turku Graduate School in Biomedical Sciences.

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  1. Department of Medical Biochemistry and Molecular Biology, University of Turku, Kiinamyllynkatu 10, 20520, Turku, Finland

    Kirsi Joronen & Eero Vuorio

  2. Departments of Medical Biochemistry and Molecular Biology and Dermatology and Medicity Research laboratory, University of Turku, Turku, Finland

    Veli-Matti Kähäri

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  1. Kirsi Joronen
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  2. Veli-Matti Kähäri
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  3. Eero Vuorio
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Correspondence to Eero Vuorio.

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Joronen, K., Kähäri, VM. & Vuorio, E. Temporospatial expression of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in mouse antigen-induced arthritis. Histochem Cell Biol 124, 535–545 (2005). https://doi.org/10.1007/s00418-005-0011-2

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