Fig. 1.

Schematic presentation of the canonical Wnt-signaling pathway and of the effect of sclerostin on bone cells. a Wnts bind to the receptor complex of frizzled (FZD) and LRP5/6, prevent the degradation of beta-catenin, and increase its accumulation in the cytoplasm; beta-catenin is translocated to the nucleus where it associates with transcription factors to control transcription of target genes in osteoblasts. b Osteocyte-produced sclerostin is transported to the bone surface and acts on osteoblasts to reduce bone formation by disabling the association of Wnts with their co-receptors and inhibiting the Wnt pathway in osteoblasts, an action facilitated by LRP4; sclerostin also stimulates the production of RANKL by neighboring osteocytes and osteoclastic bone resorption