Abstract
Bone is a dynamic tissue that must respond to developmental, repair, and remodeling cues in a rapid manner with changes in gene expression. Carefully-coordinated cycles of bone resorption and formation are essential for healthy skeletal growth and maintenance. Osteoclasts are large, multinucleated cells that are responsible for breaking down bone by secreting acids to dissolve the bone mineral and proteolytic enzymes that degrade the bone extracellular matrix. Increased osteoclast activity has a severe impact on skeletal health, and therefore, osteoclasts represent an important therapeutic target in skeletal diseases, such as osteoporosis. Progression from multipotent progenitors into specialized, terminally-differentiated cells involves carefully-regulated patterns of gene expression to control lineage specification and emergence of the cellular phenotype. This process requires coordinated action of transcription factors with co-activators and co-repressors to bring about proper activation and inhibition of gene expression. Histone deacetylases (HDACs) are an important group of transcriptional co-repressors best known for reducing gene expression via removal of acetyl modifications from histones at HDAC target genes. This review will cover the progress that has been made recently to understand the role of HDACs and their targets in regulating osteoclast differentiation and activity and, thus, serve as potential therapeutic target.
Highlights
A common misconception about the skeleton is that it is static; bone is an ever-changing organ that is remodeled through tight coupling of bone resorption followed by formation of new bone [1,2,3]
Regulation of gene expression is controlled, in part, by histone deacetylases (HDACs) [9], which are intracellular enzymes that directly affect chromatin structure, transcription factor activity [10], signaling events, and affect the activities required for bone remodeling
We focus on regulation of osteoclasts by transcriptional factors and introduce important findings on how osteoclasts are regulated by HDACs to exert bone-resorbing activity
Summary
A common misconception about the skeleton is that it is static; bone is an ever-changing organ that is remodeled through tight coupling of bone resorption followed by formation of new bone [1,2,3] These processes are performed by bone-resorbing osteoclasts and bone-forming osteoblasts. Regulation of gene expression is controlled, in part, by histone deacetylases (HDACs) [9], which are intracellular enzymes that directly affect chromatin structure, transcription factor activity [10], signaling events, and affect the activities required for bone remodeling. Understanding how these molecular and Molecules 2019, 24, 1355; doi:10.3390/molecules24071355 www.mdpi.com/journal/molecules. We will begin by discussing osteoclasts and their transcriptional factors followed by the influence of HDACs on osteoclast differentiation and activity
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