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Youlten, S.E.* ; Kemp, J.P.* ; Logan, J.G.* ; Ghirardello, E.J.* ; Sergio, C.M.* ; Dack, M.R.G.* ; Guilfoyle, S.E.* ; Leitch, V.D.* ; Butterfield, N.C.* ; Komla-Ebri, D.* ; Chai, R.C.* ; Corr, A.P.* ; Smith, J.T.* ; Mohanty, S.T.* ; Morris, J.A.* ; McDonald, M.M.* ; Quinn, J.M.W.* ; McGlade, A.R.* ; Bartonicek, N.* ; Jansson, M.* ; Hatzikotoulas, K. ; Irving, M.D.* ; Beleza-Meireles, A.* ; Rivadeneira, F.* ; Duncan, E.* ; Richards, J.B.* ; Adams, D.J.* ; Lelliott, C.J.* ; Brink, R.* ; Phan, T.G.* ; Eisman, J.A.* ; Evans, D.M.* ; Zeggini, E. ; Baldock, P.A.* ; Bassett, J.H.D.* ; Williams, G.R.* ; Croucher, P.I.*

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

Nat. Commun. 12:2444 (2021)
Publ. Version/Full Text DOI
Open Access Gold
Creative Commons Lizenzvertrag
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 × 10-22) and are associated with the polygenic diseases osteoporosis (P = 1.8 × 10-13) and osteoarthritis (P = 1.6 × 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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Publication type Article: Journal article
Document type Scientific Article
Keywords Genome-wide; R/bioconductor Package; Sclerostin Antibody; Differential Gene; Image-analysis; Bone-formation; Sost Gene; R Package; In-vitro; Osteoblast
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Quellenangaben Volume: 12, Issue: 1, Pages: , Article Number: 2444 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Translational Genomics (ITG)
Grants Department of Health
Medical Research Council
Cancer Research UK