7 Transcriptional Control of Osteoblast Differentiation

In contrast with chondrocyte differentiation, where all maturational stages are morphologically marked as well as spatially distinguishable within the growth plate, osteoblast differentiation is not marked by phenotypic changes in vivo, and osteoblasts in culture are, and remain throughout their differentiation, similar to fibroblasts. This absence of morphological features implies that one has to rely on gene expression studies to assess osteoblast differentiation. However, here again, the osteoblast has a poorly specific genetic program. Most of the proteins expressed by this cell type are also expressed in other cells, notably in fibroblasts. Another feature of osteoblast differentiation is that its embryonic layout is more complex than the events taking place once the skeleton is formed. Indeed, the developmental process by which osteoblast precursors first appear in the bone collar, begin to differentiate and then migrate within the core of the forming skeletal element along with invading blood vessels, is not observed anymore once the bones are formed. In the mature skeleton osteoblast, progenitor cells are spread out within the bone marrow and differentiate in situ. These two particularities explain for the most part why identifying the key transcriptional events required for osteoblast differentiation and function has been slower than for other cell types. However, in the last decade, these limitations have been overcome due to a combination of molecular efforts and genetic studies in mice and humans. This chapter summarizes our current knowledge about the transcriptional control of osteoblast differentiation and function (Fig. 1). CONTROL OF OSTEOBLAST DIFFERENTIATION BY RUNX2...