The regulation of osteoclast differentiation by Wnt signals

Wnt ligands activate β-catenin-dependent canonical and -independent noncanonical signaling pathways. Wnt regulates many physiological events such as the development of organs and bone metabolism. In contrast, failed signaling leads to pathological conditions including cancer and osteoporosis. Analyses of loss-of-function mutations in the low-density lipoprotein receptor-related protein (Lrp) 5 gene revealed that Lrp5 acted as a co-receptor of Wnt/β-catenin signals and positively regulated bone mass in humans and mice. Many players in Wnt signals including sclerostin, an osteocyte-derived Wnt antagonist, also have since been found to influence bone mass. Bone mass is regulated by the activities of bone-forming osteoblasts, -resorbing osteoclasts and matrix-embedded osteocytes. The roles of Wnt/β-catenin signals in osteoblastogenesis and osteoclastogenesis have been established by the findings of a large number of in vitro and in vivo studies. In contrast, the roles of noncanonical Wnt signals in bone metabolism are only now being examined. In this review, we introduced and discussed recent information on the roles of Wnt signals in bone resorption.