SOX off for bone formation Free

The vertebrate skeleton is initially laid down as a cartilaginous template by resting and proliferating chondrocytes. These cells subsequently differentiate into hypertrophic chondrocytes, which replace the cartilage in the growth plates of the long bones, ribs and vertebrae with bony tissue (endochondral ossification). Now, Takako Hattori, Klaus von der Mark and colleagues identify the SRY family transcription factor SOX9 as a negative regulator of endochondral ossification and of cartilage vascularisation and bone marrow formation (see p. 901). Sox9 is normally expressed in proliferating chondrocytes but not in hypertrophic chondrocytes. The researchers show that bone marrow formation, cartilage vascularisation and endochondral ossification are all suppressed in transgenic mice that misexpress Sox9 in hypertrophic chondrocytes. Vegfa and other markers of chondrocyte terminal differentiation are downregulated in these mice, they report. Importantly, other experiments indicate that SOX9 directly suppresses Vegfa expression by binding to SRY sites in its promoter. Thus, the researchers suggest, SOX9 downregulation in the hypertrophic zone of the growth plate is essential for endochondral bone formation.