Roles of non-canonical Wnt signaling pathways in bone resorption

Background: Wnt is a cytokine involved in the development and homeostasis of various organs. In 2001, low-density lipoprotein receptor-related protein 5 (LRP5) was identified as the gene responsible for osteoporosis pseudoglioma syndrome and regulation of bone mass. Since LRP5 belongs to the low density lipoprotein receptor family, this finding garnered the attention of researchers in the bone, mineral, and Wnt research fields. The role of Wnt in bone formation and resorption has since been extensively studied. Wnt/beta-catenin signals are known to play a role in bone resorption. The activation of these signals in osteoblast lineage cells such as osteoblasts and osteocytes induces the expression of osteoprotegerin and then inhibits osteoclast formation. Highlight: Wnt5a binds to Ror2 receptors and activates non-canonical signaling pathways, thereby promoting osteoclast differentiation and bone-resorbing activity. In contrast, Wnt16 activates non-canonical Wnt signaling in osteoclast precursor cells and suppresses the Rankl-induced activation of Nf-kappa b and Nfatcl, thereby inhibiting osteoclast differentiation. Conclusion: Wnt5a and Wnt16 tightly regulate osteoclast differentiation and function in order to maintain bone mass under physiological conditions. (C) 2018 Japanese Association for Oral Biology. Published by Elsevier B.V.