Regulation of gene expression in osteoblasts

Abstract

In recent years, much progress has been made in understanding the factors that regulate the gene expression program that underlies the induction, proliferation, differentiation, and maturation of osteoblasts. A large and growing number of transcription factors make important contributions to the precise control of osteoblast formation and function. It has become increasingly clear that these diverse transcription factors and the signals that regulate their activity cannot be viewed as discrete, separate signaling pathways. Rather, they form a highly interconnected, cooperative network that permits gene expression to be closely regulated. There has also been a substantial increase in our understanding of the mechanistic control of gene expression by cofactors such as acetyltransferases and histone deacetylases. The purpose of this review is to highlight recent progress in understanding the major transcription factors and epigenetic coregulators, including histone deacetylases and microRNAs, involved in osteoblastogenesis and the mechanisms that determine their functions as regulators of gene expression.

Figure 1. Interactions between Runx2, Histone Deacetylases and Acetyltransferases

(A) Runx2 recruits p300 or HDAC3 to target gene promoters, where they acetylate/deacetylate chromatin to regulate transcriptional activity. PTH promotes p300-Runx2 interactions and enhances gene expression. (B) BMP2 promotes acetylation and stabilization of Runx2 protein by p300, while HDAC4 and HDAC5 promote its deacetylation, ubiquitination, and proteolysis. (C) HDAC7 represses Runx2 through unknown means. BMP2 stimulates PKD1 to phosphorylate HDAC7, freeing Runx2 from HDAC7 repression. (D) Regulators of HDAC6-Runx2 interaction and the HDAC6 repressive mechanism have not been identified.