Fig. 2.

Schematic representation of sclerostin actions. Osteocyte-produced sclerostin inhibits the proliferation, differentiation, and survival of osteoblasts and reduces bone formation; it also stimulates the production of RANKL by neighboring osteocytes and bone resorption. In osteoblasts, sclerostin binds to LRP5/6 and inhibits the Wnt signaling pathway, an action facilitated by LRP4. Production of sclerostin is decreased by mechanical loading, PTH, estrogens and other factors, and antisclerostin antibodies. LRP low-density lipoprotein receptor-related protein, PTH parathyroid hormone, RANKL receptor activator of nuclear factor kappa-B ligand