Wnt and the Wnt signaling pathway in bone development and disease.

Wnt signaling affects both bone modeling, which occurs during development, and bone remodeling, which is a lifelong process involving tissue renewal. Wnt signals are especially known to affect the differentiation of osteoblasts. In this review, we summarize recent advances in understanding the mechanisms of Wnt signaling, which is divided into two major branches: the canonical pathway and the noncanonical pathway. The canonical pathway is also called the Wnt/β-catenin pathway. There are two major noncanonical pathways: the Wnt-planar cell polarity pathway (Wnt-PCP pathway) and the Wnt-calcium pathway (Wnt-Ca2+ pathway). This review also discusses how Wnt ligands, receptors, intracellular effectors, transcription factors, and antagonists affect both the bone modeling and bone remodeling processes. We also review the role of Wnt ligands, receptors, intracellular effectors, transcription factors, and antagonists in bone as demonstrated in mouse models. Disrupted Wnt signaling is linked to several bone diseases, including osteoporosis, van Buchem disease, and sclerosteosis. Studying the mechanism of Wnt signaling and its interactions with other signaling pathways in bone will provide potential therapeutic targets to treat these bone diseases. Send correspondence to: Wei Chen, Department of Pathology, University of Alabama at Birmingham, SHEL 815, 1825 University Blvd, Birmingham AL 35294-2182, USA, Tel: 205-975-2605, Fax: 205-975-4919, wechen@uab.edu. This is an un-copyedited author manuscript that has been accepted for publication in the Frontiers in Bioscience. Cite this article as it appears in the Journal of Frontiers in Bioscience. Full citation can be found by searching the Frontiers in Bioscience (Search for articles) following publication and at PubMed (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=searchD available in PMC 2014 April 25. Published in final edited form as: Front Biosci (Landmark Ed). ; 19: 379–407. N IH -P A A uhor M anscript N IH -P A A uhor M anscript N IH -P A A uhor M anscript