January 3, 2007
As a human embryo forms, most of its bones begin as cartilage and are converted into bone. This developmental transition is orchestrated by a complex network of proteins known as transcription factors, which activate the appropriate genes at the appropriate time and duration to carry out the ossification process. One of the most-studied of these transcription factors is called Runx2. Without its transcriptional oversight in the ossification process, cartilage-producing chondrocytes will not fully mature, nor will bone-producing osteoblasts differentiate. What has intrigued scientists is Runx2 is expressed in fetal progenitor cells as early as embryonic day 10, or well before its curtain call to orchestrate chondrocyte and osteoblast differentiation. This has led some to wonder if during early skeletal development other transcription factors inhibit the activity of Runx2 and hold it in check until needed. In the December 12 issue of the Proceedings of the National Academy of Sciences, NIDCR grantees and their colleagues identify this inhibitory transcription factor as Sox9. They show in laboratory and animal studies that Sox9 directly interacts with Runx2 and dominantly represses its activity. The scientists also show that this repression likely takes place early on as precursor cells commit to cartilage-producing lineages and later during the development of cartilage. Further delineating the Sox9/Runx2 interaction will help to explain the biochemical underpinnings of several human skeletal malformations and will be useful in learning to engineer replacement bone.