Abstract
Matrix metalloproteinases (MMPs) are a large group of enzymes responsible for matrix degradation. Among them, the family of gelatinases (MMP-2/gelatinase A and MMP-9/gelatinase B) is overproduced in the joints of patients with rheumatoid arthritis. Because of their degradative effects on the extracellular matrix, gelatinases have been believed to play an important role in progression and cartilage degradation in this disease, although their precise roles are yet to be defined. To clarify these roles, we investigated the development of Ab-induced arthritis, one of the murine models of rheumatoid arthritis, in MMP-2 or MMP-9 knockout (KO) mice. Surprisingly, the MMP-2 KO mice exhibited severe clinical and histologic arthritis than wild-type mice. The MMP-9 KO mice displayed milder arthritis. Recovery from exacerbated arthritis in the MMP-2 KO mice was possible by injection of wild-type fibroblasts. These results indicated a suppressive role of MMP-2 and a pivotal role of MMP-9 in the development of inflammatory joint disease.
MeSH terms
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Animals
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Antibodies, Monoclonal / administration & dosage*
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Arthritis, Rheumatoid / enzymology*
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Arthritis, Rheumatoid / genetics
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Arthritis, Rheumatoid / immunology*
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Arthritis, Rheumatoid / therapy
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Disease Models, Animal
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Disease Progression
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Dose-Response Relationship, Immunologic
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Embryo, Mammalian
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Female
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Fibroblasts / enzymology
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Fibroblasts / transplantation
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Hindlimb
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Injections, Intravenous
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Matrix Metalloproteinase 2 / deficiency
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Matrix Metalloproteinase 2 / genetics
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Matrix Metalloproteinase 2 / metabolism
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Matrix Metalloproteinase 2 / physiology*
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Matrix Metalloproteinase 9 / deficiency
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Matrix Metalloproteinase 9 / genetics
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Matrix Metalloproteinase 9 / metabolism
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Matrix Metalloproteinase 9 / physiology*
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Metalloendopeptidases / biosynthesis
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Metalloendopeptidases / genetics
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Protease Inhibitors / metabolism
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Tissue Inhibitor of Metalloproteinases / biosynthesis
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Tissue Inhibitor of Metalloproteinases / genetics
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Up-Regulation / genetics
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Up-Regulation / immunology
Substances
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Antibodies, Monoclonal
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Protease Inhibitors
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Tissue Inhibitor of Metalloproteinases
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Metalloendopeptidases
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 9