Transcriptional activation of human MMP-13 gene expression by c-Maf in osteoarthritic chondrocyte.
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.
Li
Tao
T
Department of Orthopaedics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, & Peking Union Medical College, Beijing, China.
Xiao
Jun
J
Wu
Zhihong
Z
Qiu
Guixing
G
Ding
Yaozhong
Y
D001665:Binding Sites / Q000235:genetics; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics; D006801:Humans; D053509:Matrix Metalloproteinase 13 / Q000235:genetics*; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D051257:Proto-Oncogene Proteins c-maf / Q000235:genetics*; D018808:Transcription Factor AP-1 / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics; D014162:Transfection
D004268:DNA-Binding Proteins; C495607:MAF protein, human; D051257:Proto-Oncogene Proteins c-maf; D018808:Transcription Factor AP-1; D053509:Matrix Metalloproteinase 13