The role of matrix metalloproteinase-2 and matrix metalloproteinase-9 in antibody-induced arthritis
The role of matrix metalloproteinase-2 and matrix metalloproteinase-9 in antibody-induced arthritis
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DOI：
10.4049/jimmunol.169.5.2643
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发表时间：
2002-09-01
影响因子：
4.4
通讯作者：
Suzuki, R
中科院分区：
文献类型：
--
作者：
Itoh, T;Matsuda, H;Suzuki, R
基质金属蛋白酶（MMPs）是一大类负责基质降解的酶。其中，明胶酶家族（MMP-2/明胶酶A和MMP-9/明胶酶B）在体内过量产生。类风湿性关节炎患者的关节。由于它们对细胞外基质的降解作用，明胶酶被认为在这种疾病的进展和软骨降解中起重要作用，尽管它们的确切作用尚未确定。为了阐明这些作用，我们在MMP-2或MMP-9敲除（KO）小鼠中研究了类风湿关节炎小鼠模型之一的ab诱导关节炎的发展。令人惊讶的是，MMP-2 KO小鼠比野生型小鼠表现出严重的临床和组织学关节炎。MMP-9 KO小鼠表现出较轻的关节炎。通过注射野生型成纤维细胞，可以使MMP-2 KO小鼠从加重的关节炎中恢复。这些结果表明MMP-2的抑制作用和MMP-9在炎性关节疾病的发展中起关键作用。
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.