Establishment of cell lineages involves successive differentiation steps that are controlled by specific transcription factors. A runt domain containing transcription factor Runx2 is necessary for osteoblast differentiation and bone formation. In deed, in Runx2-null mice osteoblast differentiation is arrested as both endochondral and intramembranous bone formation fail to occur.
Methods: We tried to identify osteoblast-specific genes.
Results: We have identified a novel zinc finger-containing transcription factor that we have named Osterix. In homozygous Osx-null mutant mice, osteoblast differentiation is arrested. Osx-null mutations lead to complete absence of bones formed through both endochondral and intramembranous bone formation. Normal levels of Runx2 expression in Osx-null mutants indicate that Osx is not required for Runx2 expression. No Osx transcripts are detected in the periosteum of endochondral skeletal elements of Runx2-null mice, indicating that Osx is downstream of Runx2 in the pathway of osteoblast differentiation and that Runx2 is required for Osx expression.
Conclusions: Osx is a transcription factor required for osteoblast differentiation. Type I collagen is the most abundant structural protein in vertebrates. Recent transgenic mice studies suggested that separate cis-acting elements in the proa1(I) collagen gene (Col1a1) regulated expression of reporter genes in different type I collagen producing cells. Since the osteoblast-specific element became active at a time when osteoblasts and odontoblasts first appeared in ossification centers and tooth primordia, respectively, transgenes under the control of this element serve as a unique but potent early marker of osteoblast/odontoblast differentiation. Regulation of osteoblast specific elements of Col1a1 by Runx2 and Osx will be discussed.