Fig. 4.

Different combinations of transcription factors drive tissue-specific gene expression in immature versus hypertrophic chondrocytes. The early steps of chondrogenesis, including mesenchymal condensation and the expression of chondrocyte-specific extracellular matrix proteins, are crucially dependent upon Sox-family transcription factors, including Sox9, Sox5 and Sox6 (de Crombrugghe et al., 2001; Lefebvre, 2002). By contrast, the process of chondrocyte hypertrophy is regulated by Runx2 and Runx3 (Inada et al., 1999; Kim et al., 1999; Yoshida et al., 2004), Mef2c and Mef2d (Arnold et al., 2007), and Foxa2/3 (Ionescu et al., 2012). Both direct interactions and/or regulatory relationships between these and other transcriptional regulators are displayed. See text for details. Acan, aggrecan; Col2a1, collagen, type II, α1; Col10a1, collagen, type X, α1; Mmp13, matrix metalloprotein 13; Spp1, osteopontin/bone sialoprotein 1; VEGFA, vascular endothelial growth factor A.