Abstract

Wnts transduce signals through Wnt/β-catenin pathway (canonical pathway) , in which β-catenin stimulates transcription of target genes, as well as several kinds of non-β-catenin Wnt pathways (alternative pathways) . Wnt/β-catenin pathway is essential for cell proliferation and survival, and its activity is strictly regulated by several antagonists. These antagonists inhibit Wnt signaling either in extracellular fluid, in cytoplasm, or in nucleus. Sclerosteosis and van Buchem disease are rare congenital skeletal diseases caused by inactivating mutations in genes encoding Wnt antagonists. Moreover, it has been reported that knockout mice of Wnt antagonist genes show high bone mass with increased bone formation. Therefore, Wnt antagonists are potential drug targets as bone anabolic agents.

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