Dexamethasone enhances SOX9 expression in chondrocytes

SOX9 is a transcription factor that activates type II procollagen (Col2a1) gene expression during chondrocyte differentiation. Glucocorticoids are als o known to promote chondrocyte differentiation via unknown molecular mechan isms. We therefore investigated the effects of a synthetic glucocorticoid, dexamethasone (DEX), on Sox9 gene expression in chondrocytes prepared From rib cartilage of newborn mice. Sox9 mRNA was expressed at high levels in th ese chondrocytes. Treatment with DEX enhanced Sox9 mRNA expression within 2 4 h and this effect was observed at least up to 48 h. The effect of DEX was dose dependent, starting at 0.1 nM and maximal at 10 nM. The half life of Sox9 mRNA was approximately 45 min in the presence or absence of DEX. Weste rn blot analysis revealed that DEX also enhanced the levels of SOX9 protein expression. Treatment with DEX enhanced Col2a1 mRNA expression in these ch ondrocytes and furthermore, DEX enhanced the activity of Col2-CAT (chloramp henicol acetyltransferase) construct containing a 1.6 kb intron fragment wh ere chondrocyte-specific Sry/Sox-consensus sequence is located. The enhanci ng effect of DEX was specific to SOX9, as DEX did not alter the levels of S ox6 mRNA expression. These data suggest that DEX promotes ch differentiatio n through enhancement of SOX9.