Tissue specific and vitamin D responsive gene expression in bone.

Studies of gene expression in bone have adopted a number of molecular approaches that seek to determine those cis and trans-acting factors responsible for the development and physiological regulation of this unique tissue. The majority of studies have been performed in vitro, focussing on the expression of genes such as osteocalcin, bone sialoprotein and type I collagen which demonstrate restricted or altered expression patterns in osteoblasts. These studies have demonstrated a large number of cis and trans acting factors that modulate the tissue specific and vitamin D responsive expression of these genes. These include the response elements and regions mediating basal and vitamin D dependent transcription of these genes as well as some of the transcription factors that bind to these regions and the nucleosomal organisation of these genes within a nuclear framework. In vivo studies, including the introduction of transgenes into transgenic mice, extend these in vitro observations within a physiological context. However, in part due to limitations in each approach, these in vitro and in vivo studies are yet to accurately define all the necessary cis and trans-acting factors required for tissue specific and vitamin D responsive gene expression. Advances have been made in identifying many cis-acting regions within the flanking regions of these genes that are responsible for their restricted expression patterns, but a vector incorporating all the necessary cis-acting regions capable of directing gene expression independent of integration site has not yet been described. Similarly, trans-acting factors that determine the developmental destiny of osteoblast progenitors and the restricted expression of these genes remain elusive and, despite advances in the understanding of protein-DNA interactions at vitamin D response elements contained within these genes, further intermediary factors that interact with the transcriptional machinery to modulate vitamin D responsiveness need to be identified.