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Publication : Osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease.

First Author  Youlten SE Year  2021
Journal  Nat Commun Volume  12
Issue  1 Pages  2444
PubMed ID  33953184 Mgi Jnum  J:319854
Mgi Id  MGI:6713786 Doi  10.1038/s41467-021-22517-1
Citation  Youlten SE, et al. (2021) Osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease. Nat Commun 12(1):2444
abstractText  Osteocytes are master regulators of the skeleton. We mapped the transcriptome of osteocytes from different skeletal sites, across age and sexes in mice to reveal genes and molecular programs that control this complex cellular-network. We define an osteocyte transcriptome signature of 1239 genes that distinguishes osteocytes from other cells. 77% have no previously known role in the skeleton and are enriched for genes regulating neuronal network formation, suggesting this programme is important in osteocyte communication. We evaluated 19 skeletal parameters in 733 knockout mouse lines and reveal 26 osteocyte transcriptome signature genes that control bone structure and function. We showed osteocyte transcriptome signature genes are enriched for human orthologs that cause monogenic skeletal disorders (P = 2.4 x 10(-22)) and are associated with the polygenic diseases osteoporosis (P = 1.8 x 10(-13)) and osteoarthritis (P = 1.6 x 10(-7)). Thus, we reveal the molecular landscape that regulates osteocyte network formation and function and establish the importance of osteocytes in human skeletal disease.
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