WNT7B promotes bone formation in part through mTORC1

PLoS Genet. 2014 Jan 30;10(1):e1004145. doi: 10.1371/journal.pgen.1004145. eCollection 2014 Jan.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Lineage
  • Embryo, Mammalian
  • Gene Expression Regulation, Developmental
  • Humans
  • Mechanistic Target of Rapamycin Complex 1
  • Mice
  • Multiprotein Complexes / biosynthesis
  • Multiprotein Complexes / genetics*
  • Osteoblasts / cytology
  • Osteogenesis / genetics*
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / genetics*
  • TOR Serine-Threonine Kinases / biosynthesis
  • TOR Serine-Threonine Kinases / genetics*
  • Wnt Proteins / biosynthesis
  • Wnt Proteins / genetics*
  • Wnt Signaling Pathway
  • Wnt-5a Protein


  • Multiprotein Complexes
  • Proto-Oncogene Proteins
  • Wnt Proteins
  • Wnt-5a Protein
  • Wnt5a protein, mouse
  • Wnt7b protein, mouse
  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases