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Publication : Histone H3K27 demethylase, Utx, regulates osteoblast-to-osteocyte differentiation.

First Author  Xia Y Year  2022
Journal  Biochem Biophys Res Commun Volume  590
Pages  132-138 PubMed ID  34974301
Mgi Jnum  J:319849 Mgi Id  MGI:6865173
Doi  10.1016/j.bbrc.2021.12.102 Citation  Xia Y, et al. (2022) Histone H3K27 demethylase, Utx, regulates osteoblast-to-osteocyte differentiation. Biochem Biophys Res Commun 590:132-138
abstractText  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(DeltaOcy/DeltaOcy)). Micro CT analyses showed that Utx(DeltaOcy/DeltaOcy) 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(DeltaOcy/DeltaOcy). Furthermore, Dmp1 expression and the number of osteocytes were significantly decreased in Utx(DeltaOcy/DeltaOcy). 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.
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