Regulation of bone metabolism by Wnt signals

Y Kobayashi, S Uehara, N Udagawa… - The journal of …, 2016 - academic.oup.com
Y Kobayashi, S Uehara, N Udagawa, N Takahashi
The journal of biochemistry, 2016academic.oup.com
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 …
Abstract
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.
Oxford University Press