骨细胞
成骨细胞
脱甲基酶
细胞生物学
DMP1型
细胞分化
化学
生物
表观遗传学
基因
体外
生物化学
病毒基质蛋白
作者
Yuhan Xia,Aoi Ikedo,Jiwon Lee,Tadahiro Iimura,Kenzo Inoue,Yuuki Imai
标识
DOI:10.1016/j.bbrc.2021.12.102
摘要
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 (UtxΔOcy/ΔOcy). Micro CT analyses showed that UtxΔOcy/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 UtxΔOcy/ΔOcy. Furthermore, Dmp1 expression and the number of osteocytes were significantly decreased in UtxΔOcy/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.
科研通智能强力驱动
Strongly Powered by AbleSci AI