WNT signaling, essential for many aspects of development, is among the most commonly altered pathways associated with human disease. While initially studied in cancer, dysregulation of WNT signaling has been determined to be essential for skeletal development and the maintenance of bone health throughout life. In this review, we discuss the role of Wnt signaling in bone development and disease with a particular focus on two areas. First, we discuss the roles of WNT signaling pathways in skeletal development, with an emphasis on congenital and idiopathic skeletal syndromes and diseases that are associated with genetic variations in WNT signaling components. Next, we cover a topic that has long been an interest of our laboratory, how high and low levels of WNT signaling affects the establishment and maintenance of healthy bone mass. We conclude with a discussion of the status of WNT-based therapeutics in the treatment of skeletal disease.
Keywords: Bone; LRP5; LRP6; Osteoblast; Osteoporosis; Robinow syndrome; Romosozumab; Skeletal disease; Therapeutics; Wnt.
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