title: Synovial MMP-3 and TIMP-1 levels and their correlation with cytokine expression in canine rheumatoid arthritis.
abstract: The purpose of this study was to investigate whether synovial fluid levels of matrix metalloprotease-3 (MMP-3) and tissue inhibitor of metalloprotease-1 (TIMP-1) are specifically elevated in canine rheumatoid arthritis (CRA) compared to osteoarthritic joint disorders and if these markers are correlated with a specific pattern of cytokine mRNA expression. Synovial fluid samples of 17 dogs with CRA were analysed for MMP-3 and TIMP-1 by two canine sandwich ELISA (enzyme-linked immunosorbent assay) systems. The synovial mRNA content of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-12 (IL-12), transforming growth factor-beta (TGF-beta), and interferon-gamma (IFN-gamma) was determined by RT-PCR (reverse transcription-polymerase chain reaction). Dogs with osteoarthritis (n = 50) caused by anterior cruciate ligament rupture (ACLR) were used as controls. A significant rise of MMP-3 was found in the synovial fluid of joints with CRA that could not be balanced by sufficient amounts of TIMP-1. The 30-fold surplus of MMP-3 over TIMP-1 was strongly correlated with the synovial mRNA content of IL-1, IL-12 and TGF-beta. Our results point to the potential use of the synovial levels of MMP-3 as a marker for RA in dogs.
authors.affiliation: Faculty of Veterinary Medicine, Institute of Immunology and Molecular Biology, Free University of Berlin, Philippstr 13, D-10115 Berlin, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Hegemann
authors.forename: Assefa
authors.initials: A
authors.lastname: Wondimu
authors.forename: Kirsten
authors.initials: K
authors.lastname: Ullrich
authors.forename: Michael F G
authors.initials: MF
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000662:veterinary*; D015415:Biomarkers / Q000032:analysis; D016207:Cytokines / Q000235:genetics*; D004283:Dog Diseases / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000032:analysis*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013582:Synovial Fluid / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019278:Matrix Metalloproteinase 3