Histone demethylase JMJD3 is required for osteoblast differentiation in mice.

Feng Zhang,Gerard Karsenty,Qing Xu,Longxia Xu,Charlie Degui Chen,Longyong Xu

doi:10.1038/srep13418

Abstract

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.

Highlights

During embryo development, bones form through two distinct processes: intramembranous and endochondral ossification[1]
We demonstrated that JMJD3 biochemically and genetically cooperates with RUNX2 to regulate osteoblast differentiation and bone ossification in mice
Whether JMJD3 is required for intramembranous ossification in vivo, we examined the membranous bones of E14.5–E18.5 littermates by alcian blue and alizarin S red staining

Summary

Introduction

Bones form through two distinct processes: intramembranous and endochondral ossification[1]. Some cranial bones and the lateral portion of the clavicles are formed by intramembranous ossification, during which mesenchymal progenitor cells directly differentiate into bone-forming osteoblasts. The perichondral mesenchymal cells flanking the cartilaginous template differentiate into osteoblasts and form the periosteum or cortical bone[1,2,3,4]. RUNX2 is a master regulator of osteoblast differentiation for both intramembranous and endochondral ossification[1,2,3,4]. Runx[2] null mice display a complete loss of both intramembranous and endochondral ossification with a blockage of osteoblast differentiation[6,7]. We reported that JMJD3 promoted osteoblast differentiation and bone ossification in vivo. We demonstrated that JMJD3 biochemically and genetically cooperates with RUNX2 to regulate osteoblast differentiation and bone ossification in mice

Methods

Results

Conclusion