Mesenchymal Deletion of Histone Demethylase NO66 in Mice Promotes Bone Formation

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
Qin ChenBenoit de Crombrugghe

Abstract

Our previous studies indicated that the Jumonji C (JmjC)-domain-containing NO66 is a histone demethylase with specificity for methylated histone H3K4 and H3K36. NO66 binds to the transcription factor Osterix (Osx) and inhibits its transcriptional activity in promoter assays. However, the physiological role of NO66 in formation of mammalian bones is unknown. Here, using a genetically engineered mouse model, we show that during early skeletal development, Prx1-Cre-dependent mesenchymal deletion of NO66 promotes osteogenesis and formation of both endochondral as well as intramembranous skeletal elements, leading to a larger skeleton and a high bone mass phenotype in adult mice. The excess bone formation in mice where NO66 was deleted in cells of mesenchymal origin is associated with an increase in the number of preosteoblasts and osteoblasts. Further analysis revealed that in the embryonic limbs and adult calvaria of mice with deletion of NO66 in cells of mesenchymal origin, expression of several genes including bone morphogenetic protein 2 (Bmp2), insulin-like growth factor 1 (Igf1), and osteoclast inhibitor osteoprotegerin was increased, concurrent with an increase in expression of bone formation markers such as osterix (Osx), t...Continue Reading

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Citations

Feb 13, 2019·Journal of Cellular and Molecular Medicine·Xiaoshi JiaYuhong Li
Aug 15, 2020·Current Osteoporosis Reports·Dimitrios Cakouros, Stan Gronthos
Aug 9, 2020·Journal of the American Society of Nephrology : JASN·Liping ZhangWilliam E Mitch
Aug 29, 2018·Cellular and Molecular Life Sciences : CMLS·James R BundredMathew L Coleman
Jun 30, 2019·International Journal of Molecular Sciences·Sun-Ju YiKyunghwan Kim
Dec 24, 2019·Trends in Cell Biology·Bing-Dong SuiCheng-Hu Hu
Feb 12, 2021·Frontiers in Cell and Developmental Biology·Fei XuGuobin Liu
Apr 30, 2019·Biochimica Et Biophysica Acta. Reviews on Cancer·Sangphil OhRalf Janknecht

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