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JMJD3 promotes chondrocyte proliferation and hypertrophy during endochondral bone formation in mice Free
Feng Zhang1,2, Longyong Xu1, Longxia Xu1, Qing Xu1, Dangsheng Li3, Yingzi Yang4, Gerard Karsenty5, and Charlie Degui Chen1,*
1State 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, Shanghai 200031, China
2Department of Pathology, State Key Laboratory of Cancer Biology, Xijing Hospital, Fourth Military Medical University, Shaanxi 710032, China
3Shanghai Information Center for Life Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
4National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
5Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA *Correspondence to:Charlie Degui Chen, E-mail: cdchen@sibcb.ac.cn
J Mol Cell Biol, Volume 7, Issue 1, February 2015, Pages 23-24  https://doi.org/10.1093/jmcb/mjv003
Keyword: JMJD3, RUNX2, chondrocyte, endochondral bone formation

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.