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WNT7B promotes bone formation in part through mTORC1

Chen, J. and Tu, X. and Esen, E. and Joeng, K. S. and Lin, C. and Arbeit, J. M. and Rüegg, M. A. and Hall, M. N. and Ma, L. and Long, F.. (2014) WNT7B promotes bone formation in part through mTORC1. PLoS Genetics, 10 (1). e1004145.

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Official URL: http://edoc.unibas.ch/dok/A6233700

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Abstract

WNT signaling has been implicated in both embryonic and postnatal bone formation. However, the pertinent WNT ligands and their downstream signaling mechanisms are not well understood. To investigate the osteogenic capacity of WNT7B and WNT5A, both normally expressed in the developing bone, we engineered mouse strains to express either protein in a Cre-dependent manner. Targeted induction of WNT7B, but not WNT5A, in the osteoblast lineage dramatically enhanced bone mass due to increased osteoblast number and activity; this phenotype began in the late-stage embryo and intensified postnatally. Similarly, postnatal induction of WNT7B in Runx2-lineage cells greatly stimulated bone formation. WNT7B activated mTORC1 through PI3K-AKT signaling. Genetic disruption of mTORC1 signaling by deleting Raptor in the osteoblast lineage alleviated the WNT7B-induced high-bone-mass phenotype. Thus, WNT7B promotes bone formation in part through mTORC1 activation.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Hall)
05 Faculty of Science > Departement Biozentrum > Neurobiology > Pharmacology/Neurobiology (Rüegg)
UniBasel Contributors:Hall, Michael N. and Rüegg, Markus A.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Public Library of Science
ISSN:1553-7390
e-ISSN:1553-7404
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:13 Dec 2017 12:45
Deposited On:27 Mar 2014 13:13

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