Strategic Research for Upstream Molecules, Target molecules and Co-factors of the SOX trio, the Essential Transcription Factors for Chondrogenesis

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We screened target molecules by the microarray analysis and identified 100A1 and B, transcriptional targets of SOX trio, inhibit terminal differentiation of chondrocytes. We established ATDC5-S2RD5 cells for real-time monitering of chondrogenic differentiation, using the SOX9 enhancer of Type II collagen and fluorescence reporter DsRed. Using ATDC5-S2RD5, we identified that BMP2 regulated Type II collagen expression mainly by MAPK signals rather than by SMAD signals. We also identified SNX19 as the novel molecule inducing chondrogenic differentiation by this system. For screening of upstream molecules of the SOX trio, we identified and characterized the CES6, the embryo enhancer of SOX6 by 5'RACE. By the south-western screening using the CES6, we identified p63 as the novel essential transcription factor of chondrogenic differentiaion, inducing SOX9, SOX6, type II collagen, etc. We also identified GNL3 as the upstream molecule of SOX6 and as co-facotr of SOX9 by this screening. Furthermore, we identified RUNX1, RUNX2, RUNX3 and GATA5 as the co-factors of SOX9 transactivating the type II collagen promoter.