Figure 2

Mechanism of blockade of the Wnt signalling pathway by osteocytes. Osteocytes detect changes in bone morphology through their sensitivity to mechanical forces, thereby regulating bone turnover through direct physical contact with osteoblasts. Osteocytes produce OPN, DMP, MEPE, SCL and DKK-1. The β-catenin-dependent canonical Wnt signalling pathway controls gene expression by stabilizing β-catenin in regulating a diverse array of biological processes. It is initiated by binding of appropriate Wnt ligands to the frizzled (Fz) and low-density lipoprotein receptor-related proteins 5 and 6 (LRP-5/6) and can be antagonized by secreted proteins from SCL and the DKK family, that bind with high affinity to LRP-5 or LRP-6, thereby directly prevent Wnt binding. Wnt proteins act on osteoblast precursor cells through this pathway and promote their differentiation into mature osteoblasts. In addition, they can suppress bone resorption by up-regulating OPG and down-regulating RANKL expression in mature osteoblasts, leading to a net increase in bone mass [6]. Additionally research has targeted the complex regulation of osteocyte action by expression of PTH/PTHrP receptor’s (PPR’s). Osteocyte activation of PPR leads to down-regulation of Sost and increased Wnt signalling stimulating bone formation, accompanied by up-regulation of RANKL expression and osteoclast number increasing resorption. In contrast the main effect of PPR deletion on osteocytes is reduced osteoclast and osteoblast numbers and decreased bone remodelling [7].