BoneKEy Reports | BoneKEy Watch
Wnt5a-Ror2 signaling boosts osteoclastogenesis
DOI:10.1038/bonekey.2012.90
The impact of noncanonical Wnt signaling on bone resorption is unknown. Maeda et al. used a series of in vitro cell culture studies to show that osteoclastogenesis was increased due to Wnt5a expression by osteoblast lineage cells, which signal through the receptor tyrosine kinase-like orphan receptor 2 proteins (Ror2) within osteoclast precursors.
The role of Wnt5a signalling in osteoclastogenesis was then confirmed in vivo using a type II collagen-induced arthritis mouse model. Mice that were Wnt5a knockout, or Ror2 knockout, were unable to produce osteoclasts in normal quantities, due to reduced levels of the the nuclear factor-KB ligand (RANKL).
Together, the findings suggest that the Wnt5a-Ror2 pathway could be usefully targeted in arthritis and other bone disorders.
Editor's comment: We already knew that the Wnt-β-catenin signaling pathway was a complex one, both by the number of cofactors involved and by the various target cells/functions in bone, including differentiation and activity of the osteoblastic lineage and osteocytic control of bone resorption. This brilliant set of experiments highlights that complexity, showing that Wnt5a, expressed by osteoblasts, is a coupling factor to osteoclasts that acts through Ror2. A pathogenic role in bone destruction is also demonstrated.
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