1. Histone H3K27 demethylase, Utx, regulates osteoblast-to-osteocyte differentiation.
- Author
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Xia, Yuhan, Ikedo, Aoi, Lee, Ji-Won, Iimura, Tadahiro, Inoue, Kazuki, and Imai, Yuuki
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DEMETHYLASE , *BONE growth , *KNOCKOUT mice , *OSTEOCYTES , *CELL differentiation - Abstract
Osteocytes are master regulators of skeletal homeostasis. However, little is known about the molecular mechanism of their differentiation. Epigenetic regulations, especially H3K27me3 modification, play critical roles in cell differentiation. Here, we found that H3K27me3 in the loci of osteocyte-expressing genes decreased during osteocyte differentiation and that H3K27me3 demethylase, Utx, was bound to the loci of those genes. To investigate the physiological functions of Utx in vivo , we generated late osteoblast-to-osteocyte specific Utx knockout mice using Dmp1-cre mice (Utx ΔOcy/ΔOcy ). Micro CT analyses showed that Utx ΔOcy/ΔOcy displayed osteopenic phenotypes with lower bone volume and trabecular number, and greater trabecular separation. Bone histomorphometric analysis showed that bone mineralization and formation were significantly lower in Utx ΔOcy/ΔOcy . Furthermore, Dmp1 expression and the number of osteocytes were significantly decreased in Utx ΔOcy/ΔOcy . These results suggest that Utx in Dmp1-expressing osteoblast/osteocyte positively regulates osteoblast-to-osteocyte differentiation through H3K27me3 modifications in osteocyte genes. Our results provide new insight into the molecular mechanism of osteocyte differentiation. • H3K27me3 is negatively correlated with the expression of upregulated genes during osteocyte differentiation. • Utx binds to the regulatory regions of critical osteocyte genes such as Sost , Dmp1 , Mepe and Dkk1. • Utx ΔOcy/ΔOcy exhibits osteopenic phenotype with reduced bone formation. • Utx ΔOcy/ΔOcy displays reduced Dmp1 expression and the number of osteocytes. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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