Transcriptional suppression of Sox9 expression in chondrocytes by retinoicacid

SOX9 is a transcription factor that is expressed in chondrocytes and regula tes expression of chondrocyte phenotype related genes. Expression of these genes is known to be suppressed by retinoic acid (RA). We, therefore, exami ned whether the Sox9 gene expression is regulated by RA in chondrocytes. RA treatment suppressed Sox9 mRNA expression in primary chondrocytes prepared from newborn mouse rib cartilage within 12 h and this suppression lasted a t least up to 24 h. The RA suppression of Sox9 mRNA levels was dose-depende nt starting at 0.5 muM with a maximum at 1 muM. Nuclear run-on assays revea led that RA reduced the rate of transcription of Sox9 gene. Finally, Wester n blot analysis indicated that RA suppressed SOX9 protein revels in these c hondrocytes. Furthermore, overexpression of SOX9 reversed RA suppression of Col/2a1 enhancer activity. These observations indicate that RA suppresses Sox9 gene expression in chondrocytes at least in part through transcription al events. (C) 2001 Wiley-Liss, Inc.