The relationship of cell proliferation to the temporal expression of genes characterizing a developmental sequence associated with bone cell differentiation was examined in primary diploid cultures…
It is proposed that WNT/TCF1 signaling, like bone morphogenetic protein/transforming growth factor-β signaling, activates Runx2 gene expression in mesenchymal cells for the control of osteoblast differentiation and skeletal development.
The studies establish a mechanism for BMP morphogens to selectively induce a tissue-specific phenotype and suppress alternative lineages by down-regulating multiple miRNAs that constitute an osteogenic program, thereby releasing from inhibition pathway components required for cell lineage commitment.
This work states that for many years, bone was defined anatomically and examined largely in a descriptive manner by ultrastructural analysis and by biochemical and histochemical methods, but now, complemented by an increased knowledge of molecular mechanisms that are associated with and regulate expression of genes encoding phenotypic compone...
The loss of stringent growth control in transformed osteoblasts and in osteosarcoma cells is accompanied by a deregulation of the tightly coupled relationship between proliferation and progressive expression of genes associated with bone cell differentiation.
It is determined that human ES cells remain viable after synchronization with either nocodazole or the anti‐tumor drug Paclitaxel (taxol) and have an abbreviated G1 phase of only 2.5–3 h that is significantly shorter than in somatic cells.
An overview of the concepts of tissue-specific transcriptional control mechanisms essential for development of the bone cell phenotype is presented and the specificity of Runx2 regulatory activities provides a basis for novel therapeutic strategies to correct bone disorders.
It is demonstrated that osteoblastogenesis is limited by an elaborate network of functionally tested miRNAs that directly target the osteogenic master regulator Runx2, and their effects can be reversed by the corresponding anti-miRNAs.
The biological functions of Runx factors in promoting cell fate determination and lineage progression are discussed, which include integrating ECM signaling and cues from developmental, hormonal, and signal transduction pathways by formation of complexes organized in subnuclear domains and mediating cell growth control.
Characterization of miRNAs that operate through tissue-specific transcription factors in osteoblast and osteoclast lineage cells, as well as intricate feedforward and reverse loops, has provided novel insights into the supervision of signaling pathways and regulatory networks controlling normal bone formation and turnover.