title: JMJD3 promotes chondrocyte proliferation and hypertrophy during endochondral bone formation in mice.
abstract: 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.
authors.affiliation: 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, Shanghai 200031, China Department of Pathology, State Key Laboratory of Cancer Biology, Xijing Hospital, Fourth Military Medical University, Shaanxi 710032, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: 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, Shanghai 200031, China.
authors.forename: Longyong
authors.initials: L
authors.lastname: Xu
authors.affiliation: 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, Shanghai 200031, China.
authors.forename: Longxia
authors.initials: L
authors.lastname: Xu
authors.affiliation: 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, Shanghai 200031, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Shanghai Information Center for Life Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Dangsheng
authors.initials: D
authors.lastname: Li
authors.affiliation: National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Gerard
authors.initials: G
authors.lastname: Karsenty
authors.affiliation: 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, Shanghai 200031, China cdchen@sibcb.ac.cn.
authors.forename: Charlie Degui
authors.initials: CD
authors.lastname: Chen
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D004392:Dwarfism / Q000235:genetics / Q000473:pathology; D015870:Gene Expression; D005838:Genotype; D053823:Hedgehog Proteins / Q000235:genetics; D006801:Humans; D006984:Hypertrophy; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D010012:Osteogenesis / Q000235:genetics*; D010641:Phenotype; D011485:Protein Binding; D012863:Skeleton; D014158:Transcription, Genetic
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D053823:Hedgehog Proteins; C514061:ihh protein, mouse; D056484:Jumonji Domain-Containing Histone Demethylases; C523761:Kdm6b protein, mouse
keywords: JMJD3; RUNX2; chondrocyte; endochondral bone formation