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

Scott E. Youlten, John P. Kemp, John G. Logan, Elena J. Ghirardello, Claudio M. Sergio, Michael R. G. Dack, Siobhan E. Guilfoyle, Victoria D. Leitch, Natalie C. Butterfield, Davide Komla-Ebri, Ryan C. Chai, Alexander P. Corr, James T. Smith, Sindhu T. Mohanty, John A. Morris, Michelle M. McDonald, Julian M. W. Quinn, Amelia R. McGlade, Nenad Bartonicek, Matt Jansson, Konstantinos Hatzikotoulas, Melita D. Irving, Ana Beleza-Meireles, Fernando Rivadeneira, Emma Duncan, J. Brent Richards, David J. Adams, Christopher J. Lelliott, Robert Brink, Tri Giang Phan, John A. Eisman, David M. Evans, Eleftheria Zeggini, Paul A. Baldock, J. H. Duncan Bassett (), Graham R. Williams () and Peter I. Croucher ()
Additional contact information
Scott E. Youlten: Bone Biology, Garvan Institute of Medical Research
John P. Kemp: University of Queensland Diamantina Institute, UQ
John G. Logan: Molecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London
Elena J. Ghirardello: Molecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London
Claudio M. Sergio: Bone Biology, Garvan Institute of Medical Research
Michael R. G. Dack: Molecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London
Siobhan E. Guilfoyle: Molecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London
Victoria D. Leitch: Molecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London
Natalie C. Butterfield: Molecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London
Davide Komla-Ebri: Molecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London
Ryan C. Chai: Bone Biology, Garvan Institute of Medical Research
Alexander P. Corr: Bone Biology, Garvan Institute of Medical Research
James T. Smith: Bone Biology, Garvan Institute of Medical Research
Sindhu T. Mohanty: Bone Biology, Garvan Institute of Medical Research
John A. Morris: New York Genome Center
Michelle M. McDonald: Bone Biology, Garvan Institute of Medical Research
Julian M. W. Quinn: Bone Biology, Garvan Institute of Medical Research
Amelia R. McGlade: Bone Biology, Garvan Institute of Medical Research
Nenad Bartonicek: Garvan Institute of Medical Research and The Kinghorn Cancer Centre
Matt Jansson: Viapath Genetics Laboratory, Viapath Analytics LLP, Guy’s Hospital
Konstantinos Hatzikotoulas: Institute of Translational Genomics, Helmholtz Zentrum München – German Research Center for Environmental Health
Melita D. Irving: Department of Clinical Genetics, Guy’s and St Thomas’ NHS Trust
Ana Beleza-Meireles: University Hospitals Bristol
Fernando Rivadeneira: Department of Internal Medicine, Erasmus, MC
Emma Duncan: Faculty of Life Sciences and Medicine, Department of Twin Research & Genetic Epidemiology, School of Life Course Sciences, King’s College London
J. Brent Richards: Faculty of Life Sciences and Medicine, Department of Twin Research & Genetic Epidemiology, School of Life Course Sciences, King’s College London
David J. Adams: Wellcome Sanger Institute
Christopher J. Lelliott: Wellcome Sanger Institute
Robert Brink: St Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney
Tri Giang Phan: St Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney
John A. Eisman: Bone Biology, Garvan Institute of Medical Research
David M. Evans: University of Queensland Diamantina Institute, UQ
Eleftheria Zeggini: Institute of Translational Genomics, Helmholtz Zentrum München – German Research Center for Environmental Health
Paul A. Baldock: Bone Biology, Garvan Institute of Medical Research
J. H. Duncan Bassett: Molecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London
Graham R. Williams: Molecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London
Peter I. Croucher: Bone Biology, Garvan Institute of Medical Research

Nature Communications, 2021, vol. 12, issue 1, 1-21

Abstract: Abstract 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22517-1

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DOI: 10.1038/s41467-021-22517-1

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