Regulation of bone metabolism by Wnt signals

J Biochem. 2016 Apr;159(4):387-92. doi: 10.1093/jb/mvv124. Epub 2015 Dec 28.


Wnt ligands play a central role in the development and homeostasis of various organs through β-catenin-dependent and -independent signalling. The crucial roles of Wnt/β-catenin signals in bone mass have been established by a large number of studies since the discovery of a causal link between mutations in the low-density lipoprotein receptor-related protein 5 (Lrp5) gene and alternations in human bone mass. The activation of Wnt/β-catenin signalling induces the expression of osterix, a transcription factor, which promotes osteoblast differentiation. Furthermore, this signalling induces the expression of osteoprotegerin, an osteoclast inhibitory factor in osteoblast-lineage cells to prevent bone resorption. Recent studies have also shown that Wnt5a, a typical non-canonical Wnt ligand, enhanced osteoclast formation. In contrast, Wnt16 inhibited osteoclast formation through β-catenin-independent signalling. In this review, we discussed the current understanding of the Wnt signalling molecules involved in bone formation and resorption.

Keywords: Wnt5a; Wntless; bone; osteoblast; osteoclast.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bone Resorption / metabolism*
  • Cell Differentiation / physiology
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-5 / genetics
  • Low Density Lipoprotein Receptor-Related Protein-5 / metabolism*
  • Mice
  • Mutation
  • Osteoblasts / metabolism
  • Osteoclasts / metabolism
  • Osteogenesis / physiology*
  • Osteoprotegerin / metabolism
  • Protein Transport
  • Transcription Factors / metabolism
  • Wnt Proteins / metabolism*
  • Wnt Signaling Pathway / physiology*
  • beta Catenin / metabolism


  • Low Density Lipoprotein Receptor-Related Protein-5
  • Osteoprotegerin
  • TNFRSF11B protein, human
  • Transcription Factors
  • Wnt Proteins
  • beta Catenin