Wnt/β-catenin signaling pathway plays an important role in bone metabolism. This signal is subject to strict regulation, involving endogenous soluble inhibitors. Dkk1 is a member of family of secreted protein which functions in head induction during Xenopus embryogenesis. Dkk1 forms a ternary complex with LRP5/6 and Kremen, resulting in suppression of Wnt signaling and decreased bone formation. Heterozygous knockout mice of Dkk1 show high bone mass, while transgenic mice overexpressing Dkk1 exhibit low bone mass phenotype. Anti-Dkk1 monoclonal antibody has been shown to accelerate bone formation and increase bone mineral density in various animal models and is under development as a bone-anabolic agent.
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