Transcriptional regulation of osteoblast differentiation during development

Abstract

The osteoblast is the bone-forming cell. The molecular basis of osteoblast-specific gene expression and differentiation begin to be understood. Following the characterization of OSE2, an osteoblast-specific cis-acting element present in the Osteocalcin promoter Osf2/Cbfa1, the protein that binds to OSE2, was identified. Osf2/Cbfa1 is a member of the runt family of transcription factors. Its expression is initiated in the mesenchymal condensations of the developing skeleton and is strictly restricted to cells of the osteoblast lineage thereafter. Osf2/Cbfa1 binds to and regulates the expression of multiple genes expressed in osteoblasts, and forced expression of Osf2/Cbfa1 in nonosteoblastic cells induces the expression of the principal osteoblast-specific genes. Osf2/Cbfa1 gene inactivation in mice leads to failure of mesenchymal progenitor cells to differentiate into osteoblasts. Lastly, heterozygous mutations in the Osf2/Cbfa1 gene cause Cleidocranial dysplasia in human and mice, a condition marked by generalized bone defects. These result demonstrate that Osf2/Cbfa1 is an osteoblast-specific transcriptional activator of osteoblast differentiation whose function is non redundant with the function of other gene products during development.

Akt promotes BMP2-mediated osteoblast differentiation and bone development

“…11B). Since Runx2 and Osx are produced by both chondrocytes and osteoblasts, whereas Ocn is synthesized exclusively by differentiated osteoblasts (Karsenty, 1998), we interpret these data to indicate that Akt DN interfered with osteoblast development…”

Osteoblastic differentiation of mesenchymal stem cells by mumie extract

“…Cbfa1 is a transcription factor that regulates early phases of osteoblastic differentiation [Ducy et al, 1997;Karsenty, 1998]. Pluripotent mesenchymal precursor cell line C2C12 provides a model system to study the early events of osteoblastic differentiation during bone formation [Lee et al, 2000].…”

“…Osteocalcin is present in bone matrix and osteoblasts and is a differentiation marker at a later stage of osteoblastic differentiation [Weinreb et al, 1990]. Cbfa1 is a new member of the Runt family of transcription factors, the expression of which is initiated in the mesenchymal condensations of developing skeleton and is strongly restricted to cells of the osteoblast lineage thereafter [Karsenty, 1998]. Cbfa1 induces expression of osteoblastic marker genes such as ALP, type I collagen, osteopontin, bone sialoprotein, and osteocalcin [Harada et al, 1999].…”

Effects of a novel calcium aluminate cement on the early events of the progression of osteogenic cell cultures

“…Although the role of ALP in bone formation is still not fully understood and subjected to controversies, such enzyme has been routinely used as an early marker of osteoblast differentiation (19). During bone matrix mineralization, ALP generates the inorganic phosphate needed for hydroxyapatite crystallization and might also hydrolyze pyrophosphate, a mineralization inhibitor, to facilitate mineral precipitation and growth (20).…”