Transcriptional regulation of MMP13 by Lef1 in chondrocytes

An association between Wnt/β-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-1β-mediated MMP13 regulation in mouse chondrocytes. Lef1 and β-catenin synergistically upregulated MMP13 transcription while knock-down of Lef1 using Lef1 siRNA downregulated IL-1β-mediated MMP13 expression. Lef1 binding site was mapped to the 3′ region of the MMP13 genomic locus and binding of Lef1/β-catenin to the site was confirmed by chromatin immunoprecipitation (ChIP) assays and electrophoretic mobility shift assays (EMSAs). Furthermore, Lef1/β-catenin binding to the Lef1 binding site transactivated MMP13 promoter activity. Our results suggest a pivotal role of Lef1/β-catenin in MMP13 regulation in chondrocytes, which might be associated with matrix loss of degenerated arthritic cartilage.