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  • Title: Transcriptional activation of human MMP-13 gene expression by c-Maf in osteoarthritic chondrocyte.
    Author: Li T, Xiao J, Wu Z, Qiu G, Ding Y.
    Journal: Connect Tissue Res; 2010; 51(1):48-54. PubMed ID: 20067416.
    Abstract:
    Matrix metalloproteinase (MMP)-13 has pivotal roles in the pathogenesis of Osteoarthritis (OA) and it is necessary to understand the regulatory mechanisms of MMP-13 expression. MMP-13 gene expression is regulated primarily at the transcriptional level. In this study, we investigated the role of c-maf in regulating MMP-13 transcription. Using transient transfection system with an c-maf construct, and MMP-13 promoter-luciferase constructs with specific mutations in transcription factor binding sites, we found that c-maf can significantly enhance MMP-13 promoter activity via the AP-1 site, By gene suppression with RNAi technology, we could show that c-maf downregulation leads to a reduced expression of MMP13. Chromatin immunoprecipitation assays reveal that c-maf binds to the MMP-13 gene promoter to a region of the MMP-13 promoter containing the AP-1 site. Taken together, these studies demonstrate a new level of transcriptional regulation of MMP-13 expression by the c-maf.
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