JMJD3 promotes chondrocyte proliferation and hypertrophy during endochondral bone formation in mice

被引：65

作者：

Zhang, Feng ^{[1
,2
]}

Xu, Longyong ^{[1
]}

Xu, Longxia ^{[1
]}

Xu, Qing ^{[1
]}

Li, Dangsheng ^{[3
]}

Yang, Yingzi ^{[4
]}

Karsenty, Gerard ^{[5
]}

Chen, Charlie Degui ^{[1
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol,Shanghai Key Lab Mol Andro, Shanghai 200031, Peoples R China

[2] Fourth Mil Med Univ, Xijing Hosp, Dept Pathol, State Key Lab Canc Biol, Xian 710032, Shaanxi, Peoples R China

[3] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Informat Ctr Life Sci, Shanghai 200031, Peoples R China

[4] NHGRI, NIH, Bethesda, MD 20892 USA

[5] Columbia Univ, Coll Phys & Surg, Dept Genet & Dev, New York, NY 10032 USA

来源：

JOURNAL OF MOLECULAR CELL BIOLOGY | 2015年 / 7卷 / 01期

基金：

中国国家自然科学基金;

关键词：

JMJD3; RUNX2; chondrocyte; endochondral bone formation; EMBRYONIC STEM-CELLS; HISTONE LYSINE METHYLATION; DEMETHYLASE JMJD3; H3K27; DEMETHYLASE; GENE-EXPRESSION; METHYLTRANSFERASE ACTIVITY; DEVELOPMENTAL REGULATORS; CBFA1-DEFICIENT MICE; INDIAN-HEDGEHOG; GROWTH PLATES;

D O I：

10.1093/jmcb/mjv003

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

JMJD3 (KDM6B) is an H3K27me3 demethylase and counteracts polycomb-mediated transcription repression. However, the function of JMJD3 in vivo is not well understood. Here we show that JMJD3 is highly expressed in cells of the chondrocyte lineage, especially in prehypertrophic and hypertrophic chondrocytes, during endochondral ossification. Homozygous deletion of Jmjd3 results in severely decreased proliferation and delayed hypertrophy of chondrocytes, and thereby marked retardation of endochondral ossification in mice. Genetically, JMJD3 associates with RUNX2 to promote proliferation and hypertrophy of chondrocytes. Biochemically, JMJD3 associates with and enhances RUNX2 activity by derepression of Runx2 and Ihh transcription through its H3K27me3 demethylase activity. These results demonstrate that JMJD3 is a key epigenetic regulator in the process of cartilage maturation during endochondral bone formation.

引用

页码：23 / 34

页数：12

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