Hdac-mediated control of endochondral and intramembranous ossification

Abstract

Histone deacetylases (Hdacs) remove acetyl groups (CH3CO-) from ε-amino groups in lysine residues within histones and other proteins. This posttranslational (de) modification alters protein stability, protein-protein interactions, and chromatin structure. Hdac activity plays important roles in the development of all organs and tissues, including the mineralized skeleton. Bone is a dynamic tissue that forms and regenerates by two processes: endochondral and intramembranous ossification. Chondrocytes and osteoblasts are responsible for producing the extracellular matrices of skeletal tissues. Several Hdacs contribute to the molecular pathways and chromatin changes that regulate tissue-specific gene expression during chondrocyte and osteoblast specification, maturation, and terminal differentiation. In this review, we summarize the roles of class I and class II Hdacs in chondrocytes and osteoblasts. The effects of small molecule Hdac inhibitors on the skeleton are also discussed.

Figure 1

Mammalian class I, II and IV histone deacetylases.

Figure 2. Hdacs regulate endochondral ossification

A. Summary of endochondral ossification process. B. Hdacs play distinct roles in growth plate maturation zones. Hdacs control chondrocyte maturation by regulating expression of matrix genes.

Figure 3. Hdacs regulate intramembranous bone formation

A. Summary of intramembranous bone formation. B. Hdac-mediated control of during osteoblast differentiation.