Osteogenesis involves a cascade of processes wherein mesenchymal stem cells differentiate
towards osteoblasts, strictly controlled by a number of regulatory factors. Runx2 protein is a key transcription
factor which serves as a master regulator for osteogenesis by activating the promoters of
various osteoblastic genes. Runx2 is regulated by several cofactors, including the histone deacetylase
enzymes known as HDACs. HDACs are a family of proteins that regulate gene expression and/or activity
through the mechanism of deacetylation and they can be divided into four classes, namely
classes I, II, III and IV HDACs based on their sequence identity and nuclear or cytoplasmic localization.
Knockout studies of all classes of HDACs showed their specific developmental roles. Evidence has proved Runx2 to
be a repressible target of HDACs and this interplay is found to be a crucial factor controlling osteoblast differentiation.
Further, another level of osteogenic regulation involves microRNAs (miRNAs), which are small, non-coding endogenous
molecules capable of gene silencing by partial or complete complementary binding of their seed sequences to the 3’ untranslated
region (UTR) of target mRNAs. In this study, the recent developments on identifying the function of HDACs
on Runx2 expression/activity and the impact of miRNAs on HDACs in regulation of osteogenesis are reviewed.