Wnt signals and bone metabolism

Wingless-related MMTV integration site (Wnt) family members are secreted glycoproteins with a molecular weight of approximately 40kDa, and are categorized as cytokines involved in various phases of life phenomena, such as ontogenesis, morphogenesis, and carcinogenesis. The glycoproteins are conserved in various species from C. (Caenorhabditis) elegans to mammals, and 19 types of Wnt homologs have been identified in humans. The Wnt signaling pathway is broadly classified as either a canonical or noncanonical pathway. The Wnt canonical signaling pathway stimulates bone formation, and this pathway is inhibited by Sclerostin, which is known to be produced by osteocytes and to inhibit bone formation. Because mechanical loading is reported to inhibit the production of Sclerostin in osteocytes and to enhance bone formation, osteocytes are recognized as mechanosensors in the hard tissue. Recently, clinical administration of anti-Sclerostin antibody was begun for osteoporosis. Here we outline the roles of Wnt signaling in bone formation and describe the current status of use of anti-Sclerostin antibody.