Zhang Feng, Xu Longyong, Xu Longxia, Xu Qing, Karsenty Gerard, Chen Charlie Degui
Department of Pathology, State Key Laboratory of Cancer Biology, Xijing Hospital, Fourth Military Medical University, Changle West Road, No. 169, Xi'an, 710032, China.
State Key Laboratory of Molecular Biology, Shanghai Key laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, China.
Sci Rep. 2015 Aug 25;5:13418. doi: 10.1038/srep13418.
JMJD3 (KDM6B) is an H3K27me3 demethylases and emerges as an important player in developmental processes. Although some evidence indicated the involvement of JMJD3 in osteoblast differentiation in vitro, its role as a whole in osteoblast differentiation and bone formation in vivo remains unknown. Here we showed that homozygous deletion of Jmjd3 resulted in severe delay of osteoblast differentiation and bone ossification in mice. By biochemical and genetical methods, we demonstrated that JMJD3 mediated RUNX2 transcriptional activity and cooperated with RUNX2 to promote osteoblast differentiation and bone formation in vivo. These results strongly demonstrated that JMJD3 is required for osteoblast differentiation and bone formation in mice.
JMJD3(KDM6B)是一种H3K27me3去甲基化酶,在发育过程中成为一个重要角色。尽管一些证据表明JMJD3在体外成骨细胞分化中发挥作用,但其在体内成骨细胞分化和骨形成中的整体作用仍不清楚。在此我们表明,Jmjd3基因的纯合缺失导致小鼠成骨细胞分化和骨化严重延迟。通过生化和遗传学方法,我们证明JMJD3介导RUNX2的转录活性,并与RUNX2协同促进体内成骨细胞分化和骨形成。这些结果有力地证明,JMJD3是小鼠成骨细胞分化和骨形成所必需的。