Wnt signaling: A win for bone

Wnt signaling plays a central role in many processes during embryonic development and in later stages of life. At least three distinct wnt signaling pathways have been described. In 2001, evidence was obtained from genetic studies on some rare hereditary conditions, that the canonical wnt signaling pathway plays an important role in bone formation. Functional studies and experimental analysis of relevant animal models confirmed the anabolic effect of wnt signaling by modulating the differentiation, the proliferation, the activity and finally the apoptosis of (pre)osteoblasts and osteocytes. More recently, also non-canonical wnt signaling was shown to play a role in bone formation. Since there is currently a major lack of anabolic therapeutic agents for the prevention and treatment of osteoporosis this signaling pathway deserves major attention. A big concern, however, is the pleiotropic function of the pathway that needs to be taken into account in order to avoid unwanted side-effects. Preliminary data are already indicating that this might be achieved by targeting sclerostin, a bone-specific extracellular antagonist of canonical wnt signaling. (C) 2008 Elsevier Inc. All rights reserved.