Cloning of the gene for interstitial collagenase-3 (matrix metalloproteinase-13) from rabbit synovial fibroblasts: differential expression with collagenase-1 (matrix metalloproteinase-1)
Cloning of the gene for interstitial collagenase-3 (matrix metalloproteinase-13) from rabbit synovial fibroblasts: differential expression with collagenase-1 (matrix metalloproteinase-1)
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DOI：
10.1042/bj3310341
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发表时间：
1998-04-01
影响因子：
4.1
通讯作者：
Brinckerhoff, CE
中科院分区：
文献类型：
--
作者：
Vincenti, MP;Coon, CI;Brinckerhoff, CE
软骨、骨和间质间质主要由I、II和III型间质胶原组成，由金属蛋白酶（MMP）家族的三种成员胶原酶-1 （MMP-1）、胶原酶-2 （MMP-8）和胶原酶-3 （MMP-13）重塑。MMP-1和MMP-13可能直接促进疾病进展，因为它们在类风湿关节炎和骨关节炎患者中是诱导的。关节炎疾病模型中MMP-1和MMP-13基因调控的研究一直存在问题，因为通常使用的小鼠和大鼠只具有MMP-13的同源物。本研究表明，与小鼠和大鼠相比，家兔具有与人类MMP-1和MMP-13不同的同源基因。此外，兔MMP-13在软骨细胞和滑膜成纤维细胞中与MMP-1同时表达，以响应细胞因子白介素-1和肿瘤坏死因子- α或磷脂酯PMA。诱导MMP-13的时间过程比诱导MMP-1的时间过程更快、更短暂，说明这两种胶原酶的表达调节机制不同。我们从滑膜成纤维细胞中克隆了兔MMP-13基因，并证明兔基因与人MMP-13的同源性高于小鼠间质胶原酶。再加上小鼠和大鼠不具有与人类MMP-1同源的事实，我们的数据表明，兔子为研究间质胶原酶在结缔组织疾病（如类风湿关节炎和骨关节炎）中的作用提供了合适的模型。
Cartilage, bone and the interstitial stroma, composed largely of the interstitial collagens, types I, II and III, are remodelled by three members of the metalloproteinase (MMP) family, collagenase-1 (MMP-1), collagenase-2 (MMP-8) and collagenase-3 (MMP-13). MMP-1 and MMP-13 may contribute directly to disease progression, since they are induced in patients with rheumatoid arthritis and osteoarthritis. The study of MMP-1 and MMP-13 gene regulation in models of arthritic disease has been problematic because mice and rats, which are typically used, only possess a homologue of MMP-13. Here we show that in contrast with mice and rats, rabbits possess distinct genes homologous to human MMP-1 and MMP-13. Furthermore, rabbit MMP-13 is expressed simultaneously with MMP-1 in chondrocytes and synovial fibroblasts in response to the cytokines interleukin-1 and tumour necrosis factor-alpha, or the phorbol ester PMA. The time course of MMP-13 induction is more rapid and transient than that of MMP-1, suggesting that distinct mechanisms regulate the expression of these two collagenases. We have cloned the rabbit MMP-13 gene from synovial fibroblasts and demonstrated that the rabbit gene shares greater homology with human MMP-13 than does the mouse interstitial collagenase. Together with the fact that mice and rats do not possess a homologue to human MMP-1, our data suggest that the rabbit provides an appropriate model for studying the roles of interstitial collagenases in connective-tissue diseases, such as rheumatoid arthritis and osteoarthritis.