Transcriptional regulation of MMP13 by Lef1 in chondrocytes.
An association between Wnt/beta-catenin signaling and MMP13 expression has been reported but there has been little information about the underlying mechanism. Here, we investigated the role of Lef1 in IL-1beta-mediated MMP13 regulation in mouse chondrocytes. Lef1 and beta-catenin synergistically upregulated MMP13 transcription while knock-down of Lef1 using Lef1 siRNA downregulated IL-1beta-mediated MMP13 expression. Lef1 binding site was mapped to the 3' region of the MMP13 genomic locus and binding of Lef1/beta-catenin to the site was confirmed by chromatin immunoprecipitation (ChIP) assays and electrophoretic mobility shift assays (EMSAs). Furthermore, Lef1/beta-catenin binding to the Lef1 binding site transactivated MMP13 promoter activity. Our results suggest a pivotal role of Lef1/beta-catenin in MMP13 regulation in chondrocytes, which might be associated with matrix loss of degenerated arthritic cartilage.
Yun
Kangsun
K
Department of Life Sciences, Gwangju Institute of Science and Technology, 1 Oryong-dong, Puk-ku, Gwangju 500-712, Republic of Korea.
Im
Sin-Hyeog
SH
D000818:Animals; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism*; D051379:Mice; D015533:Transcriptional Activation / Q000502:physiology*
C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse