Transcriptional activation of human MMP-13 gene expression by c-Maf in osteoarthritic chondrocyte.

Publisher: Informa Healthcare Country of Publication: England NLM ID: 0365263 Publication Model: Print Cited Medium: Internet ISSN: 1607-8438 (Electronic) Linking ISSN: 03008207 NLM ISO Abbreviation: Connect Tissue Res Subsets: MEDLINE

Publication: London : Informa Healthcare
Original Publication: New York, Gordon and Breach Science Publishers.

Cartilage, Articular/*metabolism ; Chondrocytes/*metabolism ; Matrix Metalloproteinase 13/*genetics ; Osteoarthritis/*genetics ; Osteoarthritis/*metabolism ; Proto-Oncogene Proteins c-maf/*genetics; Binding Sites/genetics ; Cartilage, Articular/pathology ; Cartilage, Articular/physiopathology ; Chondrocytes/cytology ; DNA-Binding Proteins/genetics ; Humans ; Osteoarthritis/physiopathology ; Promoter Regions, Genetic/genetics ; Transcription Factor AP-1/genetics ; Transcriptional Activation/genetics ; Transfection

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.

0 (DNA-Binding Proteins)
0 (MAF protein, human)
0 (Proto-Oncogene Proteins c-maf)
0 (Transcription Factor AP-1)
EC 3.4.24.- (Matrix Metalloproteinase 13)

Date Created: 20100114 Date Completed: 20100406 Latest Revision: 20100113

20240829

10.3109/03008200902989104

20067416