WNT7B Promotes Bone Formation in Part Through MTORC1

Overview

Journal PLoS Genet

Specialty Genetics

Date 2014 Feb 6

PMID 24497849

Citations 89

Authors

Jianquan Chen

Xiaolin Tu

Emel Esen

Kyu Sang Joeng

Congxin Lin

Jeffrey M Arbeit

Markus A Ruegg

Michael N Hall

Liang Ma

Fanxin Long

Affiliations

Soon will be listed here.

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.

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